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Keratoacanthoma of the vulva
GYNECOLOGIC
ONCOLOGY
21, 118-123 (1985)
Keratoacanthoma RONALD M. RHATIGAN, *Department of Pathology, Pathology, University & Gynecology, University
M.D.,*
of the Vulva AND ROBERT C. Nuss M.D.t
University of Florida College of Medicine and Department Hospital of Jacksonville; and fDepartment of Obstetrics of Florida College of Medicine and Gynecologic Oncology, University Hospital of Jacksonville
of
Received March 20, 1984 A 65year-old white woman noted a “pea-sized” lump of the right labium majus. At the initial examination a few weeks later, the mass was 1.5 cm in maximum diameter. An excisional biopsy was interpreted as well-differentiated squamous cell carcinoma. The biopsy material was subsequently reviewed prior to recommended radical surgery. Upon review, the lesion was interpreted as a keratoacanthoma. No further surgery was performed and the patient has remained free of recurrent disease for over 2 years. This case is presented in an effort to alert gynecologic oncologists and pathologists of the possibility of this lesion occurring on the vulva. 0 1985 Academic Press. Inc.
INTRODUCTION
Keratoacanthoma is a benign squamous tumor of skin usually occurring in sun-exposed areas of the middle-aged and elderly and that clinically and histologically closely resembles a squamous cell carcinoma. Its clinical course is characterized by a rapid, sometimes alarming growth phase, over a period of weeks or a few months, followed by involution over a period of several more months. The tumor has a distinctive clinical appearance as a circular or oval, nodular, raised (hemispherical), sharply demarcated mass with a central, keratinfilled crater on the surface (see Fig. 1). The lesion has thus been likened in its appearance to a giant molluscum contagiosum or a “volcano with a stopper of hardened lava in its central crater” [l]. Clinically and histologically, the main differential is between keratoacanthoma and low-grade squamous cell carcinoma. The histologic appearance is usually distinctive and can be easily recognized, but only if the entire lesion has been removed or if the biopsy is taken in a manner that allows the overall low-power configuration of the lesion to be discerned [l]. However, at times, invasive properties of the squamous epthelium may be present and lead to an erroneous diagnosis of squamous cell carcinoma. Even when histologic evidence of invasion is present in keratoacanthoma, the behavior is not malignant and no metastases from histologically proven keratoacanthoma have been reported [2]. 118 0090-8258185 $1.50 Copyright All rights
0 1985 by Academic Press, Inc. of reproduction in any form reserved
CASE
REPORTS
119
FIG. 1. A close-up view of a rather typical keratoacanthoma occurring on the forehead. Gross photos of the patient in this report were not available but this photograph depicts the usual features, i.e., a sharply circumscribed, raised nodular mass with a central crater or umbilication.
The authors record the only example of a keratoacanthoma occurring in the vulvar skin hoping to alert gynecologists and gynecologic pathologists to a benign tumor which can be mistaken clinically and histologically for a well-differentiated squamous cell carcinoma. CASE REPORT: N.S.
The patient was a 65year-old gravida 0, white woman who was approximately 17 years postmenopausal. She had her last regular gynecologic examination in early 198 1. In February, 1982 the patient noticed a painless “pea-sized” lump in her right labium majus. There was no irritation or pruritus associated with the lump. The lesion progressed in size and in early April 1982 an excisional biopsy was performed at another hospital. The amount of skin excised was an elipse measuring 2 x 1.5 x 1 cm. The lesion was described as 1.5 cm in diameter with a superficial, central “ulceration.” The lateral and deep excisional margins of the specimen were free of tumor and the interpretation was that of a “well-differentiated squamous cell carcinoma.” The patient first presented to our hospital in early June, 1982 for evaluation and further therapy of the “squamous cell carcinoma” of the vulva. The patient
120
RHATIGAN
AND
NUSS
gave no history of diabetes, granulomatous disease, hormonal therapy, previous vulvar lesions, chronic vulvar irritation, pruritus, or use of topical medication to the vulvar area. Physical examination revealed a 2 cm, well-healed incision on the posterior half of the right labium majus. This area was normal to palpation without evidence of induration, nodularity, or ulceration. There was no palpable regional adenopathy and on pelvic examination the vagina and cervix appeared normal. The uterus was palpably normal and mobile. There were no adnexal masses or pelvic induration. Prior to planning any further therapeutic measures, histologic material was requested from the hospital where the diagnosis of well-differentiated squamous cell carcinoma had been made. Received from that hospital was one H & E slide and an accompanying protocol identifying the patient and indicating that the slide was indeed, from that patient. Later, paraffin blocks were requested and obtained from the referring hospital. Because of features noted in Figs. 2 and 3 the lesion was interpreted as a keratoacanthoma. After this diagnosis no further therapy was recommended. The patient remains in good health and has been followed at regular intervals. The vulva has remained normal to inspection and palpation. Colposcopic examination of the vulvar area has revealed no abnormal epithelial changes. Toluidine staining followed by acetic acid clearance demonstrates no abnormal uptake of the dye. Papanicolaou scrapings of the vagina and cervix also are normal.
FIG. 2. A low-power overview of a cross section of the entire tumor. The central keratin-tilled crater can be seen near the surface. (It appears covered by surface epthelium because the section is slightly “off center.“) Beneath the crater and radiating from it are irregular nests of squamous epithelium that are fairly well demarcated at their borders. (Hematoxylin & eosin, x 75.)
CASE
REPORTS
view of the deep margin of the keratoacanthoma. These are irregular FIG. 3. A higher-power and varying sized nests of well-differentiated squamous epithelium. Isolated areas such as this one, if seen alone and not in the overall context of the tumor, could be mistaken for well-differentiated squamous cell carcinoma. (Hematoxylin & eosin, x75.)
DISCUSSION
Although mainly occurring in light-skinned patients in sun-exposed areas [3], keratoacanthomas have been reported in all races and in many skin sites [4], as well as mucous membranes [5,61. The incidence of this tumor is difficult to assess because many cases have undoubtedly been classified as squamous cell carcinomas. It does seem clear that basal cell carcinoma and actinic keratoses are much more common and squamous cell carcinoma is probably more common [l]. The etiology is unknown, but a viral cause is suspected by some [7]. Its occurrence in sun-exposed areas suggests that ultraviolet radiation may play a role in the etiology. Chemical tumorigenesis must also be considered in view of studies showing an increased incidence of the tumor in pitch and tar workers
[a. Single lesions are the rule. However, multiple lesions sometime occur and a rare “eruptive” form has been reported where “thousands” of lesions are present [3]. Keratoacanthoma does not arise from preexisting lesions such as keratoses, but arises de ~OVO probably from the hair follicle though this site of origin would not explain its occurrence on mucous membranes [2,31. It grows rather rapidly over a short period of time, usually 6 to 8 weeks. The lesion may cause alarm in the patient and in the physician who is not familiar with its history and clinical appearance, especially when the growth is even more rapid, i.e., full growth in
122
RHATIGAN
AND
NUSS
only 2 to 3 weeks. Keratoacanthomas regress if left in place [1,2]. However, because of their rapid growth and alarming appearance nearly all lesions are excised. The diagnosis of keratoacanthoma is largely one based on gross appearance and low-power microscopic pattern and the overall organization of the lesion. The individual cellular details are very similar, if not identical to a well-differentiated squamous cell carcinoma. Therefore, if the entire lesion is excised, the diagnosis is usually relatively easy for the pathologist or dermatopathologist familiar with this lesion, because the overall pattern can be recognized. If only a biopsy is taken from the lesion and its overall configuration and pattern cannot be well appreciated, the diagnosis is very difficult, and under these circumstances, many keratoacanthomas could and perhaps should be diagnosed as well-differentiated squamous cell carcinomas. Table 1 may be useful for the differentiation from squamous cell carcinoma. Although keratoacanthomas are most common in sun-exposed skin, they have been reported in almost all parts of the body except for the vulva. A perianal keratoacanthoma has been reported [9]. The occurrence of keratoacanthoma on the labia is not surprising, especially when one considers that most other “tumors of the skin” have been reported on the vulva. Although keratoacanthoma is undoubtedly a rare lesion of the vulva, its true incidence is probably unknown, since, other cases may have been misinterpreted as well-differentiated squamous cell carcinoma. Surface nodular lesions of the vulva of recent onset and with rapid growth which have a central “ulcerated” or umbilicated opening on the surface should alert the gynecologist to the possibility of keratoacanthoma. Complete excision is recommended since this will enable the pathologist to see the overall configuration of the lesion in the histologic sections. This along TABLE CLINICAL
DIFFERENTIATION
Factor Rate of growth Relative size (for duration) Average age of onset Spontaneous involution Shape Central portion of tumor Borders Resemblance to molluscum contagiosum Surrounding skin Lymph node involvement Progression Origin on mucosae
BETWEEN
1
KERATOACANTHOMAS
AND
Keratoacanthoma
SQUAMOUS
CELL
CARCINOMAS
Squamous cell carcinoma
Relatively faster (weeks) Large 55 years Characteristically occurs Crateriform; exophytic Keratotic plug Well-circumscribed Often
Relatively slower (months) Small 70 years Rarely, if ever, occurs Irregular; exophytic or endophytic Necrotic ulcer with crust Often ill-defined Seldom
Often normal Absent Reaches maximum size, then does not progress further Rare
Often shows “precancerous”
a After Bowman and Pinkus, Arch.
Parho/.
60, 19
(1955).
change
Occurs
Tendency to progress indefinitely Common
CASE
with the clinical information the accurate diagnosis.
provided
123
REPORTS
by the gynecologist
will usually
assure
REFERENCES 1. Kopf, A. W. Keratoacanthoma, clinical aspects, in Cancer ofthe skin (R. Andrade, S. L. Gumport, G. L. Popkin, and T. D. Rees, Eds.), Saunders, Philadelphia, pp. 775-781 (1976). 2. Ackerman, A. B. Histopathology of keratoacanthoma, in Cancer offhe skin (R. Andrade, S. L. Gumport, G. L. Popkin, and T. D. Rees, Eds.), Saunders, Philadelphia, pp. 781-796 (1976). 3. Swartz, R. A. The keratoacanthoma: A review, J. Surg. Oncol. 12, 305-317 (1979). 4. Lever, W. F., and Schaumburg-Lever, G. K. Keratoacanthoma, in Histoparhology of the skin, Lippincott, Philadelphia, 6th ed., pp. 506-509 (1983). 5. Freeman, K., Cloud, T., and Knox, J. Keratoacanthoma of the conjuctiva, Arch. Ophthalmol. 65, 817-819 (1961). 6. Helsham, R. W., and Buchanan, G. Keratoacanthoma of the oral cavity, Oral surg. 13, 844-849 (1960). 7. Zelickson, A. S., and Lynch, F. W. Electron microscopy of virus-like particles in a keratoacanthoma, J. Invest. Dermatol. 37, 79-83 (1961). 8. Ghadially, F. N., Burton, B. W., and Kerridge, B. W. The etiology of keratoacanthoma, Cancer 16, 603-611 (1963). 9. Elliott, G. B., and Fisher, B. K. Perianal keratoacanthoma, Arch. Dermatol. 95, 81-82 (1967).
ONCOLOGY
21, 118-123 (1985)
Keratoacanthoma RONALD M. RHATIGAN, *Department of Pathology, Pathology, University & Gynecology, University
M.D.,*
of the Vulva AND ROBERT C. Nuss M.D.t
University of Florida College of Medicine and Department Hospital of Jacksonville; and fDepartment of Obstetrics of Florida College of Medicine and Gynecologic Oncology, University Hospital of Jacksonville
of
Received March 20, 1984 A 65year-old white woman noted a “pea-sized” lump of the right labium majus. At the initial examination a few weeks later, the mass was 1.5 cm in maximum diameter. An excisional biopsy was interpreted as well-differentiated squamous cell carcinoma. The biopsy material was subsequently reviewed prior to recommended radical surgery. Upon review, the lesion was interpreted as a keratoacanthoma. No further surgery was performed and the patient has remained free of recurrent disease for over 2 years. This case is presented in an effort to alert gynecologic oncologists and pathologists of the possibility of this lesion occurring on the vulva. 0 1985 Academic Press. Inc.
INTRODUCTION
Keratoacanthoma is a benign squamous tumor of skin usually occurring in sun-exposed areas of the middle-aged and elderly and that clinically and histologically closely resembles a squamous cell carcinoma. Its clinical course is characterized by a rapid, sometimes alarming growth phase, over a period of weeks or a few months, followed by involution over a period of several more months. The tumor has a distinctive clinical appearance as a circular or oval, nodular, raised (hemispherical), sharply demarcated mass with a central, keratinfilled crater on the surface (see Fig. 1). The lesion has thus been likened in its appearance to a giant molluscum contagiosum or a “volcano with a stopper of hardened lava in its central crater” [l]. Clinically and histologically, the main differential is between keratoacanthoma and low-grade squamous cell carcinoma. The histologic appearance is usually distinctive and can be easily recognized, but only if the entire lesion has been removed or if the biopsy is taken in a manner that allows the overall low-power configuration of the lesion to be discerned [l]. However, at times, invasive properties of the squamous epthelium may be present and lead to an erroneous diagnosis of squamous cell carcinoma. Even when histologic evidence of invasion is present in keratoacanthoma, the behavior is not malignant and no metastases from histologically proven keratoacanthoma have been reported [2]. 118 0090-8258185 $1.50 Copyright All rights
0 1985 by Academic Press, Inc. of reproduction in any form reserved
CASE
REPORTS
119
FIG. 1. A close-up view of a rather typical keratoacanthoma occurring on the forehead. Gross photos of the patient in this report were not available but this photograph depicts the usual features, i.e., a sharply circumscribed, raised nodular mass with a central crater or umbilication.
The authors record the only example of a keratoacanthoma occurring in the vulvar skin hoping to alert gynecologists and gynecologic pathologists to a benign tumor which can be mistaken clinically and histologically for a well-differentiated squamous cell carcinoma. CASE REPORT: N.S.
The patient was a 65year-old gravida 0, white woman who was approximately 17 years postmenopausal. She had her last regular gynecologic examination in early 198 1. In February, 1982 the patient noticed a painless “pea-sized” lump in her right labium majus. There was no irritation or pruritus associated with the lump. The lesion progressed in size and in early April 1982 an excisional biopsy was performed at another hospital. The amount of skin excised was an elipse measuring 2 x 1.5 x 1 cm. The lesion was described as 1.5 cm in diameter with a superficial, central “ulceration.” The lateral and deep excisional margins of the specimen were free of tumor and the interpretation was that of a “well-differentiated squamous cell carcinoma.” The patient first presented to our hospital in early June, 1982 for evaluation and further therapy of the “squamous cell carcinoma” of the vulva. The patient
120
RHATIGAN
AND
NUSS
gave no history of diabetes, granulomatous disease, hormonal therapy, previous vulvar lesions, chronic vulvar irritation, pruritus, or use of topical medication to the vulvar area. Physical examination revealed a 2 cm, well-healed incision on the posterior half of the right labium majus. This area was normal to palpation without evidence of induration, nodularity, or ulceration. There was no palpable regional adenopathy and on pelvic examination the vagina and cervix appeared normal. The uterus was palpably normal and mobile. There were no adnexal masses or pelvic induration. Prior to planning any further therapeutic measures, histologic material was requested from the hospital where the diagnosis of well-differentiated squamous cell carcinoma had been made. Received from that hospital was one H & E slide and an accompanying protocol identifying the patient and indicating that the slide was indeed, from that patient. Later, paraffin blocks were requested and obtained from the referring hospital. Because of features noted in Figs. 2 and 3 the lesion was interpreted as a keratoacanthoma. After this diagnosis no further therapy was recommended. The patient remains in good health and has been followed at regular intervals. The vulva has remained normal to inspection and palpation. Colposcopic examination of the vulvar area has revealed no abnormal epithelial changes. Toluidine staining followed by acetic acid clearance demonstrates no abnormal uptake of the dye. Papanicolaou scrapings of the vagina and cervix also are normal.
FIG. 2. A low-power overview of a cross section of the entire tumor. The central keratin-tilled crater can be seen near the surface. (It appears covered by surface epthelium because the section is slightly “off center.“) Beneath the crater and radiating from it are irregular nests of squamous epithelium that are fairly well demarcated at their borders. (Hematoxylin & eosin, x 75.)
CASE
REPORTS
view of the deep margin of the keratoacanthoma. These are irregular FIG. 3. A higher-power and varying sized nests of well-differentiated squamous epithelium. Isolated areas such as this one, if seen alone and not in the overall context of the tumor, could be mistaken for well-differentiated squamous cell carcinoma. (Hematoxylin & eosin, x75.)
DISCUSSION
Although mainly occurring in light-skinned patients in sun-exposed areas [3], keratoacanthomas have been reported in all races and in many skin sites [4], as well as mucous membranes [5,61. The incidence of this tumor is difficult to assess because many cases have undoubtedly been classified as squamous cell carcinomas. It does seem clear that basal cell carcinoma and actinic keratoses are much more common and squamous cell carcinoma is probably more common [l]. The etiology is unknown, but a viral cause is suspected by some [7]. Its occurrence in sun-exposed areas suggests that ultraviolet radiation may play a role in the etiology. Chemical tumorigenesis must also be considered in view of studies showing an increased incidence of the tumor in pitch and tar workers
[a. Single lesions are the rule. However, multiple lesions sometime occur and a rare “eruptive” form has been reported where “thousands” of lesions are present [3]. Keratoacanthoma does not arise from preexisting lesions such as keratoses, but arises de ~OVO probably from the hair follicle though this site of origin would not explain its occurrence on mucous membranes [2,31. It grows rather rapidly over a short period of time, usually 6 to 8 weeks. The lesion may cause alarm in the patient and in the physician who is not familiar with its history and clinical appearance, especially when the growth is even more rapid, i.e., full growth in
122
RHATIGAN
AND
NUSS
only 2 to 3 weeks. Keratoacanthomas regress if left in place [1,2]. However, because of their rapid growth and alarming appearance nearly all lesions are excised. The diagnosis of keratoacanthoma is largely one based on gross appearance and low-power microscopic pattern and the overall organization of the lesion. The individual cellular details are very similar, if not identical to a well-differentiated squamous cell carcinoma. Therefore, if the entire lesion is excised, the diagnosis is usually relatively easy for the pathologist or dermatopathologist familiar with this lesion, because the overall pattern can be recognized. If only a biopsy is taken from the lesion and its overall configuration and pattern cannot be well appreciated, the diagnosis is very difficult, and under these circumstances, many keratoacanthomas could and perhaps should be diagnosed as well-differentiated squamous cell carcinomas. Table 1 may be useful for the differentiation from squamous cell carcinoma. Although keratoacanthomas are most common in sun-exposed skin, they have been reported in almost all parts of the body except for the vulva. A perianal keratoacanthoma has been reported [9]. The occurrence of keratoacanthoma on the labia is not surprising, especially when one considers that most other “tumors of the skin” have been reported on the vulva. Although keratoacanthoma is undoubtedly a rare lesion of the vulva, its true incidence is probably unknown, since, other cases may have been misinterpreted as well-differentiated squamous cell carcinoma. Surface nodular lesions of the vulva of recent onset and with rapid growth which have a central “ulcerated” or umbilicated opening on the surface should alert the gynecologist to the possibility of keratoacanthoma. Complete excision is recommended since this will enable the pathologist to see the overall configuration of the lesion in the histologic sections. This along TABLE CLINICAL
DIFFERENTIATION
Factor Rate of growth Relative size (for duration) Average age of onset Spontaneous involution Shape Central portion of tumor Borders Resemblance to molluscum contagiosum Surrounding skin Lymph node involvement Progression Origin on mucosae
BETWEEN
1
KERATOACANTHOMAS
AND
Keratoacanthoma
SQUAMOUS
CELL
CARCINOMAS
Squamous cell carcinoma
Relatively faster (weeks) Large 55 years Characteristically occurs Crateriform; exophytic Keratotic plug Well-circumscribed Often
Relatively slower (months) Small 70 years Rarely, if ever, occurs Irregular; exophytic or endophytic Necrotic ulcer with crust Often ill-defined Seldom
Often normal Absent Reaches maximum size, then does not progress further Rare
Often shows “precancerous”
a After Bowman and Pinkus, Arch.
Parho/.
60, 19
(1955).
change
Occurs
Tendency to progress indefinitely Common
CASE
with the clinical information the accurate diagnosis.
provided
123
REPORTS
by the gynecologist
will usually
assure
REFERENCES 1. Kopf, A. W. Keratoacanthoma, clinical aspects, in Cancer ofthe skin (R. Andrade, S. L. Gumport, G. L. Popkin, and T. D. Rees, Eds.), Saunders, Philadelphia, pp. 775-781 (1976). 2. Ackerman, A. B. Histopathology of keratoacanthoma, in Cancer offhe skin (R. Andrade, S. L. Gumport, G. L. Popkin, and T. D. Rees, Eds.), Saunders, Philadelphia, pp. 781-796 (1976). 3. Swartz, R. A. The keratoacanthoma: A review, J. Surg. Oncol. 12, 305-317 (1979). 4. Lever, W. F., and Schaumburg-Lever, G. K. Keratoacanthoma, in Histoparhology of the skin, Lippincott, Philadelphia, 6th ed., pp. 506-509 (1983). 5. Freeman, K., Cloud, T., and Knox, J. Keratoacanthoma of the conjuctiva, Arch. Ophthalmol. 65, 817-819 (1961). 6. Helsham, R. W., and Buchanan, G. Keratoacanthoma of the oral cavity, Oral surg. 13, 844-849 (1960). 7. Zelickson, A. S., and Lynch, F. W. Electron microscopy of virus-like particles in a keratoacanthoma, J. Invest. Dermatol. 37, 79-83 (1961). 8. Ghadially, F. N., Burton, B. W., and Kerridge, B. W. The etiology of keratoacanthoma, Cancer 16, 603-611 (1963). 9. Elliott, G. B., and Fisher, B. K. Perianal keratoacanthoma, Arch. Dermatol. 95, 81-82 (1967).