Journal of Cutaneous Pathology 1978: 4: 342-348
Aggressive Histological Features of Keratoacanthoma IVO p. JANECKA, M.D.,' MARIANNE WOLFF, M.D.,= GEORGE F. CRIKELAIR, M.D.' AND BARD COSMAN, M.D." 'Associate in Plastic Surgery, ^Associate Professor of Surgical Pathology, 'Professor of Clinical Surgery," Associate Clinical Professor of Surgery* Thirty-nine keratoacanthomas from 35 patients have heen studied, six of which showed perineural, and one vascular, invasion. Thus far, their aggressive histological behavior has not been paralleled by a similar clinical course. However, continued close follow-up is essential. (Received for publication May 26. 1977)
Keratoacanthoma is a relatively uncommon No. 2) were rc-excised following histological skin tumor which has been categorized as evidence of squamous cells within the either benign (Ayes 1948, Calnan & Haber perineural spaces at the margins of the 1955, Ramselaar & van der Meer 1976) or excision. This was demonstrated by the malignant (Jackson 1969). We have observed India Ink technique (Crikelair & Lattes perineural invasion in six keratoacanthomas 1967). In one case (Case No. 1) the perias well as vascular invasion in one of these neural invasion was shown to be present at a lesions. This report is designed to alert distance of over 2 cm from the tumor margin physicians to these relatively unfamUiar (Fig. 2). The specimens were fixed in histological features which may cause Bouin's solution. Serial sections. 6iim concern for possible future change in the thick, were obtained from each tumor and stained using the following techniques: clinical behavior of such a skin tumor. Hematoxylin Phloxin and Safran, Luxol Fast Blue and Masson's Trichrome, as detailed in Material and Methods the Armed Forces Institute of Pathology Manual of Histological Staining methods Thirty-nine keratoacanthomas from 35 (Luna 1968). patients were examined in the Surgical Pathology Laboratory of the Columbia Presbyterian Medical Center from 1964Results and Discussion 1974 (Fig. 1). Six of the 39 lesions demonstrated perineural invasion by the neoplastic This peculiar skin lesion was apparently squamous cells (Table 1) with vascular described in 1888 by Hutchinson and the invasion found, additionally, in one of the term "Keratoacanthoma" seems to have six cases (Case No. 6). All keratoacan- been first used by Freudenthal in 1936 thomas with perineural invasion were (Hutchinson 1888, Hjorth 1960). Since then treated by excision and primary closure. there have been numerous reports describing Two of the six lesions (Case No. 1 and Case keratoacanthomas as either an entirely *From the Department of Surgery (Plastic) and the Department of Pathology (Surgical) of the Presbyterian Hospital and College of Physicians & Surgeons, Columbia University, New York, U.S.A.
AGGRESSIVE HISTOLOGY IN KERATOACANTHOMA
343
3
Fig. 1. Distribution of 39 Cases of Keratoacanthoma. Head and Neck Region: 25 cases. Scalp 3, Cheek 7, Temple 1, Nose 5, Ears 3, Lips 4, Eyelid 1, Neck 1. Trunk and Extremities: 14 cases. Shoulder 1, Buttock 1, Chest 3, Hand 3, Back 2, Legs 4. benign "self-healing" skin tumor or a metastasizing neoplasm (Ayres 1948, Calnan & Haber 1955, Jackson 1969, Ramselaar & van der Meer 1976). Most keratoacanthomas appear on exposed areas of skin. Keratoacanthomas arising on mucous membranes are extremely rare (Svirsky et al. 1977). The lesion is found almost exclusively in middle aged or older persons but it has been reported in children (Price et al 1974). The general configuration of keratoacanthoma is well described in the literature (Rook & Champion 1963). However, metastatic carcinoma to the skin from other organs may clinically imitate
keratoacanthoma (Fig. 3). Since there are no clinical or gross characteristics to indicate the depth of invasion, which might help to predict the future behavior of the neoplasm, careful histological analysis is essential. In view of the characteristic crateriform architectural pattern of growth of this tumor (Fig. 4) it is easy to understand the difficulties encountered in analyzing small biopsies taken from different zones of the same tumor. If an exeisional biopsy is not feasible, a cross-sectional incisional biopsy through the center of the tumor, including also normal tissue at either end, may be advisable. This also allows the pathologist to
JANECKA ET AL.
344
L[-S10N
Fig. 2. Schematic illustration of the extent of perineural spread by squamous ceUs in Case 1. ( Histologically documented nerve involvement by squamous cells 2 cm from the tumor margins). Table 1 Summary of Data in Six cases of Keratoacanthomas with Perineural Invasion Case
Age
Sex
Lesion location
Lesion sire (cm)
Chnical course
Follow-up (years)
L
45
M
Nasal Ala
2.5
6
2.
56
M
Upper Lip
2
3. 4.
51 72
F F
Sternum Nasal Ala
4 1
5.
86 73
F M
Temple Shoulder
4 5
Positive margins. Reexcision demonstrated perineural invasion 2 cm away from tumor. No recurrence after complete excision. Positive surgical margins foUowed by reexcision without recurrence. Excision; no recurrence Complete excision except for an involved nerve at the deepest margin; no recurrence Excision; no recurrence Excision; no recurrence
6.
8 6 6
7 4
AGGRESSIVE HISTOLOGY IN KERATOACANTHOMA
Fig. 3. Scalp metastasis (anow) from squamous cell eareinoma of lungs.
© Fig. 4. Characteristic appearance of keratoacanthoma (Hematoxylin, Phloxin and Safran X 12).
345
346
JANECKA ET AL.
Fig. 5. Intravascular invasion by squamous cells (V-vein; Trichrome X 107).
study the depth of invasion throughout the entire width of the neoplasm and possibly to make an attempt to determine the relationship between neoplastic cells and nerve fibers. The histological differentiation between keratoacanthoma and squamous cell carcinoma has been summarized recently by Chalet etaL (1975). Perineural invasion by keratoacanthoma has been observed before (Baptista 1964, Pinkus & Mehregan 1976). Perineural and vascular invasion (Figs. 5-8) in our cases was associated with keratoacanthoma extending below the dermis. In our material there appeared to be two types of nerve involvement by keratoacanthoma. In one, the nerve was involved by the advancing front of the neoplastic tumor cells (Fig. 6). In the other, tumor cells were found as isolated islands around nerves, away from the main tumor mass (Figs. 7 and 8). There were no gross features distinguishing
keratoacanthoma with nerve and vascular invasion. Our observation of aggressive histological features in keratoacanthoma is a disturbing fact but the clinical course does not indicate true biological aggressiveness. Prolonged clinical observation of such cases is essential to rule out possible future changes in their behavior. However, to date, after an observation period ranging from 4 to 8 years none of our cases has metastasized to the lymph nodes nor has this complication been reported in cases acceptable as keratoacanthoma. In many respects this situation is similar to that of verucous carcinoma of mucous membranes (Derrian et al. 1973), a tumor characterized by a bulky, exophytic primary growth composed of very well differentiated squamous cells. Only focal, inconspicuous areas of anaplasia and superficial invasion, as well as occasional perineural involvement, can be found.
AGGRESSIVE HISTOLOGY IN KERATOACANTHOMA
347
• * . * •
Fig 6 Advancing squamous cells involving peripheral nerve (N) cut longitudinally, surrounded by less well differentiated squamous epithelial cells. The dark mass in the upper left field is keratin in a focus of better differentiated squamous cells. Luxol Fast Blue X 240.
Lymph node metastases in verrucous carcinoma occur with the utmost rarity. Acknowledgements
The authors wish to express their appreciation for the helpful advice received from Raffaele Lattes, M.D., Director of Surgical Pathology; to G. Kaye, M.D., and Mrs. J. Spivack for preparation of the photomicrographs, and to Ms. K. Herczig for preparation of this manuscript.
References
Ayres, S. Jr. (1948) Squamous Cell Epithelioma (Self Healing Type). Archives of Dermatology and Sypholology 58. 584. Baptista, A. V. B. P. (1964) Querato-Aeanthoma: contribution para o sen estudo anatoma-clinico. Coimbra Editors Ltd., Portugal.
Calnan, C. D. & Haber, J. (1955) Molluscum Sebacum. Journal of Pathology and Bacteriology 69. 61. Chalet, M. D., Connors, R. C. & Ackerman, A. B. (1975) Squamous Cell Carcinoma vs. Keratoacanthoma: Criteria for Histological Differentiation. Journal of Dermatological Surgery 1, 16. Crikelair, G. F. & Lattes, R. (1967) A Useful Method to Determine the Adequacy of Surgical Resection of Skin Lesions. In: Transactions of the Fourth International Congress of Plastic & Reconstruction Surgery, pp. 117121, Rome. Derrian, S. D. E., Butkin, F. L. & Ecchecarrion, R. A. (1973) Perineural Invasion and Anapiastic Transformation of'Verrucous Carinoma. Cancer 32, 395. Hjorth, H. (1960) Keratoacanthoma: A historical note. British Journal of Dermatology 72, 292. Hutchinson, J. A. (1888) Smaller Atlas of Illustrations of Clinical Surgery. Transactions ofthe Pathology Society, London. 40, 275. Jackson, I. J. (1969) Diagnostic Problems of Keratoacanthoma. Lancet 1,490.
lANFCKA FT AL,
348
Fig. 7. A nerve bundle (or possibly a nerve end organ) surrounded by neoplastic squamous cells (N-nerve) Hematoxylin Phloxin and Safran X 80. Luna, L. G. (ed) (1968) Manual of Histological Staining Methods of the Armed Forces Institute of Pathology, pp. 39-40, 9 4 - 9 5 . Third Edition, The Blakiston Division, McGraw-Hill Book Company, N.Y. Pinkus, H. & Mehregan, A. H. (1976) A Guide to Dermatohistopathology. New York, AppletonCentury-Crofts. Price, E., Biro, L. & Cheu, Ch. (1974) Solitary Keratoacanthoma in a child. American Journal of Diseases of Children 128, 110. Ramselaar, C. G. & van der Meer, J. B. (1976) Spontaneous Regression of Keratoacanthoma in yidLix. Acta Dermatovener. (Stockholm) 56, 245. Rook, A. & Champion, R. H. (1963) Keratoacanthoma, NIH Monograph No. 10 Conference: Biology of Cutaneous Cancer. Washington, D.C. Svirsky, J. H., Freedman, P. D. & Lumerman, J. (1977) Solitary Intraoral Keratoacanthoma. Oral Surgery. Oral Medicine, Oral Pathology 43, 116. •
•
.
^
•
'
•
.
,
Fig. 8. Perineural invasion away from the main tumor mass (N-nerve or possibly a nerve end
organ). Hematoxylin, Phloxin and Safran X 94.
Address: Ivo P. Janecka, M.D. Dept. of Surgery (Plastic) Presbyterian Hospital Columbia University New York, N. Y.
U.S.A.
Aggressive Histological Features of Keratoacanthoma IVO p. JANECKA, M.D.,' MARIANNE WOLFF, M.D.,= GEORGE F. CRIKELAIR, M.D.' AND BARD COSMAN, M.D." 'Associate in Plastic Surgery, ^Associate Professor of Surgical Pathology, 'Professor of Clinical Surgery," Associate Clinical Professor of Surgery* Thirty-nine keratoacanthomas from 35 patients have heen studied, six of which showed perineural, and one vascular, invasion. Thus far, their aggressive histological behavior has not been paralleled by a similar clinical course. However, continued close follow-up is essential. (Received for publication May 26. 1977)
Keratoacanthoma is a relatively uncommon No. 2) were rc-excised following histological skin tumor which has been categorized as evidence of squamous cells within the either benign (Ayes 1948, Calnan & Haber perineural spaces at the margins of the 1955, Ramselaar & van der Meer 1976) or excision. This was demonstrated by the malignant (Jackson 1969). We have observed India Ink technique (Crikelair & Lattes perineural invasion in six keratoacanthomas 1967). In one case (Case No. 1) the perias well as vascular invasion in one of these neural invasion was shown to be present at a lesions. This report is designed to alert distance of over 2 cm from the tumor margin physicians to these relatively unfamUiar (Fig. 2). The specimens were fixed in histological features which may cause Bouin's solution. Serial sections. 6iim concern for possible future change in the thick, were obtained from each tumor and stained using the following techniques: clinical behavior of such a skin tumor. Hematoxylin Phloxin and Safran, Luxol Fast Blue and Masson's Trichrome, as detailed in Material and Methods the Armed Forces Institute of Pathology Manual of Histological Staining methods Thirty-nine keratoacanthomas from 35 (Luna 1968). patients were examined in the Surgical Pathology Laboratory of the Columbia Presbyterian Medical Center from 1964Results and Discussion 1974 (Fig. 1). Six of the 39 lesions demonstrated perineural invasion by the neoplastic This peculiar skin lesion was apparently squamous cells (Table 1) with vascular described in 1888 by Hutchinson and the invasion found, additionally, in one of the term "Keratoacanthoma" seems to have six cases (Case No. 6). All keratoacan- been first used by Freudenthal in 1936 thomas with perineural invasion were (Hutchinson 1888, Hjorth 1960). Since then treated by excision and primary closure. there have been numerous reports describing Two of the six lesions (Case No. 1 and Case keratoacanthomas as either an entirely *From the Department of Surgery (Plastic) and the Department of Pathology (Surgical) of the Presbyterian Hospital and College of Physicians & Surgeons, Columbia University, New York, U.S.A.
AGGRESSIVE HISTOLOGY IN KERATOACANTHOMA
343
3
Fig. 1. Distribution of 39 Cases of Keratoacanthoma. Head and Neck Region: 25 cases. Scalp 3, Cheek 7, Temple 1, Nose 5, Ears 3, Lips 4, Eyelid 1, Neck 1. Trunk and Extremities: 14 cases. Shoulder 1, Buttock 1, Chest 3, Hand 3, Back 2, Legs 4. benign "self-healing" skin tumor or a metastasizing neoplasm (Ayres 1948, Calnan & Haber 1955, Jackson 1969, Ramselaar & van der Meer 1976). Most keratoacanthomas appear on exposed areas of skin. Keratoacanthomas arising on mucous membranes are extremely rare (Svirsky et al. 1977). The lesion is found almost exclusively in middle aged or older persons but it has been reported in children (Price et al 1974). The general configuration of keratoacanthoma is well described in the literature (Rook & Champion 1963). However, metastatic carcinoma to the skin from other organs may clinically imitate
keratoacanthoma (Fig. 3). Since there are no clinical or gross characteristics to indicate the depth of invasion, which might help to predict the future behavior of the neoplasm, careful histological analysis is essential. In view of the characteristic crateriform architectural pattern of growth of this tumor (Fig. 4) it is easy to understand the difficulties encountered in analyzing small biopsies taken from different zones of the same tumor. If an exeisional biopsy is not feasible, a cross-sectional incisional biopsy through the center of the tumor, including also normal tissue at either end, may be advisable. This also allows the pathologist to
JANECKA ET AL.
344
L[-S10N
Fig. 2. Schematic illustration of the extent of perineural spread by squamous ceUs in Case 1. ( Histologically documented nerve involvement by squamous cells 2 cm from the tumor margins). Table 1 Summary of Data in Six cases of Keratoacanthomas with Perineural Invasion Case
Age
Sex
Lesion location
Lesion sire (cm)
Chnical course
Follow-up (years)
L
45
M
Nasal Ala
2.5
6
2.
56
M
Upper Lip
2
3. 4.
51 72
F F
Sternum Nasal Ala
4 1
5.
86 73
F M
Temple Shoulder
4 5
Positive margins. Reexcision demonstrated perineural invasion 2 cm away from tumor. No recurrence after complete excision. Positive surgical margins foUowed by reexcision without recurrence. Excision; no recurrence Complete excision except for an involved nerve at the deepest margin; no recurrence Excision; no recurrence Excision; no recurrence
6.
8 6 6
7 4
AGGRESSIVE HISTOLOGY IN KERATOACANTHOMA
Fig. 3. Scalp metastasis (anow) from squamous cell eareinoma of lungs.
© Fig. 4. Characteristic appearance of keratoacanthoma (Hematoxylin, Phloxin and Safran X 12).
345
346
JANECKA ET AL.
Fig. 5. Intravascular invasion by squamous cells (V-vein; Trichrome X 107).
study the depth of invasion throughout the entire width of the neoplasm and possibly to make an attempt to determine the relationship between neoplastic cells and nerve fibers. The histological differentiation between keratoacanthoma and squamous cell carcinoma has been summarized recently by Chalet etaL (1975). Perineural invasion by keratoacanthoma has been observed before (Baptista 1964, Pinkus & Mehregan 1976). Perineural and vascular invasion (Figs. 5-8) in our cases was associated with keratoacanthoma extending below the dermis. In our material there appeared to be two types of nerve involvement by keratoacanthoma. In one, the nerve was involved by the advancing front of the neoplastic tumor cells (Fig. 6). In the other, tumor cells were found as isolated islands around nerves, away from the main tumor mass (Figs. 7 and 8). There were no gross features distinguishing
keratoacanthoma with nerve and vascular invasion. Our observation of aggressive histological features in keratoacanthoma is a disturbing fact but the clinical course does not indicate true biological aggressiveness. Prolonged clinical observation of such cases is essential to rule out possible future changes in their behavior. However, to date, after an observation period ranging from 4 to 8 years none of our cases has metastasized to the lymph nodes nor has this complication been reported in cases acceptable as keratoacanthoma. In many respects this situation is similar to that of verucous carcinoma of mucous membranes (Derrian et al. 1973), a tumor characterized by a bulky, exophytic primary growth composed of very well differentiated squamous cells. Only focal, inconspicuous areas of anaplasia and superficial invasion, as well as occasional perineural involvement, can be found.
AGGRESSIVE HISTOLOGY IN KERATOACANTHOMA
347
• * . * •
Fig 6 Advancing squamous cells involving peripheral nerve (N) cut longitudinally, surrounded by less well differentiated squamous epithelial cells. The dark mass in the upper left field is keratin in a focus of better differentiated squamous cells. Luxol Fast Blue X 240.
Lymph node metastases in verrucous carcinoma occur with the utmost rarity. Acknowledgements
The authors wish to express their appreciation for the helpful advice received from Raffaele Lattes, M.D., Director of Surgical Pathology; to G. Kaye, M.D., and Mrs. J. Spivack for preparation of the photomicrographs, and to Ms. K. Herczig for preparation of this manuscript.
References
Ayres, S. Jr. (1948) Squamous Cell Epithelioma (Self Healing Type). Archives of Dermatology and Sypholology 58. 584. Baptista, A. V. B. P. (1964) Querato-Aeanthoma: contribution para o sen estudo anatoma-clinico. Coimbra Editors Ltd., Portugal.
Calnan, C. D. & Haber, J. (1955) Molluscum Sebacum. Journal of Pathology and Bacteriology 69. 61. Chalet, M. D., Connors, R. C. & Ackerman, A. B. (1975) Squamous Cell Carcinoma vs. Keratoacanthoma: Criteria for Histological Differentiation. Journal of Dermatological Surgery 1, 16. Crikelair, G. F. & Lattes, R. (1967) A Useful Method to Determine the Adequacy of Surgical Resection of Skin Lesions. In: Transactions of the Fourth International Congress of Plastic & Reconstruction Surgery, pp. 117121, Rome. Derrian, S. D. E., Butkin, F. L. & Ecchecarrion, R. A. (1973) Perineural Invasion and Anapiastic Transformation of'Verrucous Carinoma. Cancer 32, 395. Hjorth, H. (1960) Keratoacanthoma: A historical note. British Journal of Dermatology 72, 292. Hutchinson, J. A. (1888) Smaller Atlas of Illustrations of Clinical Surgery. Transactions ofthe Pathology Society, London. 40, 275. Jackson, I. J. (1969) Diagnostic Problems of Keratoacanthoma. Lancet 1,490.
lANFCKA FT AL,
348
Fig. 7. A nerve bundle (or possibly a nerve end organ) surrounded by neoplastic squamous cells (N-nerve) Hematoxylin Phloxin and Safran X 80. Luna, L. G. (ed) (1968) Manual of Histological Staining Methods of the Armed Forces Institute of Pathology, pp. 39-40, 9 4 - 9 5 . Third Edition, The Blakiston Division, McGraw-Hill Book Company, N.Y. Pinkus, H. & Mehregan, A. H. (1976) A Guide to Dermatohistopathology. New York, AppletonCentury-Crofts. Price, E., Biro, L. & Cheu, Ch. (1974) Solitary Keratoacanthoma in a child. American Journal of Diseases of Children 128, 110. Ramselaar, C. G. & van der Meer, J. B. (1976) Spontaneous Regression of Keratoacanthoma in yidLix. Acta Dermatovener. (Stockholm) 56, 245. Rook, A. & Champion, R. H. (1963) Keratoacanthoma, NIH Monograph No. 10 Conference: Biology of Cutaneous Cancer. Washington, D.C. Svirsky, J. H., Freedman, P. D. & Lumerman, J. (1977) Solitary Intraoral Keratoacanthoma. Oral Surgery. Oral Medicine, Oral Pathology 43, 116. •
•
.
^
•
'
•
.
,
Fig. 8. Perineural invasion away from the main tumor mass (N-nerve or possibly a nerve end
organ). Hematoxylin, Phloxin and Safran X 94.
Address: Ivo P. Janecka, M.D. Dept. of Surgery (Plastic) Presbyterian Hospital Columbia University New York, N. Y.
U.S.A.
