Practical Radiation Oncology (2015) 5, 203–206
www.practicalradonc.org
Teaching Case
Eruptive keratoacanthomas after radiation therapy for keratoacanthoma centrifugum marginatum Daniel P. Lindsay BS a , Jordan Kharofa MD a, b , Marianne Junck MD a , Edit Olasz MD a , J. Frank Wilson MD a,⁎ a
Department of Radiation Oncology, The Medical College of Wisconsin, Milwaukee, Wisconsin Department of Radiation Oncology, University of Cincinnati, Cincinnati, Ohio
b
Received 27 September 2014; revised 27 October 2014; accepted 28 October 2014
Introduction
Case presentation
Keratoacanthomas are crateriform squamous proliferations commonly accepted as a variant of well-differentiated squamous cell carcinoma (SCC). Typically, keratoacanthomas demonstrate rapid growth that causes local tissue destruction followed by spontaneous resolution with residual scarring. There are several morphological variants of keratoacanthomas, including solitary, multiple, grouped, and keratoacanthoma centrifugum marginatum (KCM). KCM is characterized by progressive peripheral tumor expansion with the ability to grow up to 30 cm in diameter. Because of their destructive capabilities and rare reports of metastasis, 1 keratoacanthomas require definitive treatment. Currently accepted treatment options for keratoacanthomas include surgical excision, radiation therapy, oral acitretin, and oral or intralesional chemotherapy. 2,3 We report a patient with a history of multiple keratoacanthomas not associated with Ferguson-Smith disease who underwent radiation treatment for a large KCM. The primary tumor resolved completely, but the patient subsequently erupted with multiple keratoacanthomas within the well-defined field of radiation treatment.
A 61-year-old white female presented because of a history of multiple keratoacanthomas. The patient had a history of at least 10 previous keratoacanthomas within the past year located on the extremities. The patient’s previous keratoacanthomas were treated with surgical excision, with local recurrence of some of the tumors. The patient’s medical history was also significant for diabetes mellitus complicated by end-stage renal disease that required dialysis. The patient had no family history of keratoacanthomas or other skin cancer. At presentation, the patient had 3 keratoacanthomas on her right forearm, approximately 4 mm each. Treatment with 5-fluorouracil chemotherapy wraps and acitretin 10 mg daily was initiated. At follow-up, the discrete keratoacanthomas had evolved into a 4.0 cm × 3.5 cm crateriform pink tumor with central ulceration consistent with KCM (Fig 1). Histopathology showed SCC with keratoacanthoma features (Fig 2). She underwent radiation therapy to a total dose of 6050 cGy with a combination of megavoltage and orthovoltage photon radiation. She received 5250 cGy in 22 fractions using 6 MV x-ray beam therapy followed by an 800 cGy orthovoltage x-ray boost (100 kilovolt peak [kVp]) in 4 fractions (Figs 3, 4, and 5). The patient was treated 4 days per week because of her hemodialysis schedule. The KCM responded well, with complete resolution; however, during the final week
Conflicts of interest: None. ⁎ Corresponding author. Medical College of Wisconsin, Department of Radiation Oncology, 9200 W Wisconsin Ave, Milwaukee, WI 53226. E-mail address: [email protected] (J. Frank Wilson).
http://dx.doi.org/10.1016/j.prro.2014.10.011 1879-8500/© 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
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Practical Radiation Oncology: May-June 2015
Figure 3 Setup for radiation therapy. (For color version, see online at www.practicalradonc.org.)
Discussion
of radiation treatment, the patient developed 10 discrete, nontender keratotic nodules within the field of treatment (Fig 6). There were no new nodules anywhere outside the radiation field. Biopsy of a representative nodule confirmed SCC, keratoacanthoma type. Tissue cultures were obtained and were negative. As initially planned, acitretin was increased from 10 mg daily to the goal dose of 20 mg daily. The patient was treated with 5-fluorouracil chemotherapy wraps and intralesional chemotherapy to individual keratoacanthomas on the right arm. Intralesional bleomycin was used initially, followed by 5 weekly treatments with intralesional 5-fluorouracil. All keratoacanthomas responded well, and there were no recurrences at 2-month follow-up (Fig 7).
Keratoacanthomas are a variant of SCC. Although keratoacanthomas usually spontaneously resolve, local destruction, disfiguring scarring, and rare reports of metastasis mandate definitive treatment of all morphological subtypes. Multiple treatment options exist for the treatment of keratoacanthomas, including surgical excision, radiation therapy, oral acitretin, and oral or intralesional chemotherapy. Although radiation therapy is often an effective treatment option, our patient exemplifies the rare occurrence of eruptive keratoacanthomas after radiation treatment. There are few previous reports in the literature of eruptive keratoacanthomas after radiation therapy. Shaw et al 4 described a 51-year-old woman who underwent radiation therapy for an unresectable SCC involving the left maxillary sinus and both ethmoidal sinuses, with extension through both orbital walls. The patient was treated with both megavoltage x-ray and electron beam radiation with a total dose of 6600 cGy. Two weeks after the first radiation
Figure 2 Well-differentiated squamous cell carcinoma with a focal vague crater filled with keratin debris (hematoxylin and eosin, original magnification × 40). (For color version, see online at www.practicalradonc.org.)
Figure 4 Setup for orthovoltage boost with 2 mm aluminum half-value layer shield. (For color version, see online at www. practicalradonc.org.)
Figure 1 Keratoacanthoma centrifugum marginatum on the right forearm. (For color version, see online at www. practicalradonc.org.)
Practical Radiation Oncology: May-June 2015
Eruptive keratoacanthomas after RT
205
Figure 5 Orthovoltage treatment setup. (For color version, see online at www.practicalradonc.org.)
treatment, the patient developed a histologically proven keratoacanthoma on the lower lip. Three weeks after the completion of radiation treatment, she erupted with numerous keratoacanthomas on the central face. She was treated successfully with oral isotretinoin with a starting dose of 2 mg/kg per day. Robertson et al 5 reported a 49-year-old male patient with a history of Ferguson-Smith disease with severe exacerbation followed by radiation treatment for an SCC of the nasal vestibule. The primary SCC resolved after a total radiation dose of 5400 cGy; however, 2 months after the patient completed therapy, he developed multiple
Figure 6 Multiple crateriform keratotic nodules within welldefined erythema corresponding to the field of radiation. Notice the resolution of the primary keratoacanthoma centrifugum marginatum. (For color version, see online at www. practicalradonc.org.)
Figure 7 Resolving keratoacanthomas after oral acitretin, 5fluorouracil chemotherapy wraps, and intralesional chemotherapy. (For color version, see online at www.practicalradonc.org.)
keratoacanthomas within the radiation field. The patient was treated successfully with acitretin 60 mg daily. In a study of families with Ferguson-Smith disease, D’Alessandro et al 6 described 2 patients as experiencing aggravation of their disease by radiation therapy. FergusonSmith, which is also known as multiple self-healing squamous epithelioma, is an autosomal dominant skin cancer disorder characterized by multiple self-healing skin tumors that resemble keratoacanthoma. One patient was treated successfully with surgical excision that required major reconstructive surgery after intralesional interferon alpha/2B therapy failed. The second was treated successfully with acitretin 50 mg daily. The radiation dose used in these patients was not reported. The etiology regarding the effects of radiation on the development of multiple eruptive keratoacanthomas and the overall risk are unknown. Interestingly, in our patient, like those similarly reported, the primary tumor resolved completely before the eruption of multiple keratoacanthomas. Eruptive keratoacanthoma should be considered in patients who develop similar clinical findings after radiation treatment for keratoacanthoma. The decision to use radiation therapy for treatment of patients with a history of multiple keratoacanthomas should be considered with caution because of the unknown risk of eruptive keratoacanthomas within the field of radiation treatment. In this clinical scenario, a reasonable treatment approach for the eruptive keratoacanthomas is acitretin combined with intralesional chemotherapy. This treatment combination has been successful in multiple patients, 3-6 including the present case.
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References 1. Hodak E, Jones RE, Ackerman AB. Solitary keratoacanthoma is a squamous-cell carcinoma: Three examples with metastases. Am J Dermatopathol. 1993;15:332-342. 2. Bogner PN, Cheney RT, Zeitouni NC. Giant keratoacanthoma: Case report and review of the English literature. Am J Dermatopathol. 2014;36:252-257. 3. Kirby JS, Miller CJ. Intralesional chemotherapy for nonmelanoma skin cancer: A practical review. J Am Acad Dermatol. 2010;63:689-702.
Practical Radiation Oncology: May-June 2015 4. Shaw JC, Storrs FJ, Everts E. Multiple keratoacanthomas after megavoltage radiation therapy. J Am Acad Dermatol. 1990;23(pt 2): 1009-1011. 5. Robertson SJ, Bashir SJ, Pichert G, Robson A, et al. Severe exacerbation of multiple self-healing squamous epithelioma (Ferguson-Smith disease) with radiotherapy, which was successfully treated with acitretin. Clin Exp Dermatol. 2010;35(4):e100-e102. 6. D’Allessandro M, Coats SE, Morley SM, et al. Multiple self-healing squamous epithelioma in different ethnic groups: More than a founder mutation disorder? J Invest Dermatol. 2007;127(10):2336-2344.
www.practicalradonc.org
Teaching Case
Eruptive keratoacanthomas after radiation therapy for keratoacanthoma centrifugum marginatum Daniel P. Lindsay BS a , Jordan Kharofa MD a, b , Marianne Junck MD a , Edit Olasz MD a , J. Frank Wilson MD a,⁎ a
Department of Radiation Oncology, The Medical College of Wisconsin, Milwaukee, Wisconsin Department of Radiation Oncology, University of Cincinnati, Cincinnati, Ohio
b
Received 27 September 2014; revised 27 October 2014; accepted 28 October 2014
Introduction
Case presentation
Keratoacanthomas are crateriform squamous proliferations commonly accepted as a variant of well-differentiated squamous cell carcinoma (SCC). Typically, keratoacanthomas demonstrate rapid growth that causes local tissue destruction followed by spontaneous resolution with residual scarring. There are several morphological variants of keratoacanthomas, including solitary, multiple, grouped, and keratoacanthoma centrifugum marginatum (KCM). KCM is characterized by progressive peripheral tumor expansion with the ability to grow up to 30 cm in diameter. Because of their destructive capabilities and rare reports of metastasis, 1 keratoacanthomas require definitive treatment. Currently accepted treatment options for keratoacanthomas include surgical excision, radiation therapy, oral acitretin, and oral or intralesional chemotherapy. 2,3 We report a patient with a history of multiple keratoacanthomas not associated with Ferguson-Smith disease who underwent radiation treatment for a large KCM. The primary tumor resolved completely, but the patient subsequently erupted with multiple keratoacanthomas within the well-defined field of radiation treatment.
A 61-year-old white female presented because of a history of multiple keratoacanthomas. The patient had a history of at least 10 previous keratoacanthomas within the past year located on the extremities. The patient’s previous keratoacanthomas were treated with surgical excision, with local recurrence of some of the tumors. The patient’s medical history was also significant for diabetes mellitus complicated by end-stage renal disease that required dialysis. The patient had no family history of keratoacanthomas or other skin cancer. At presentation, the patient had 3 keratoacanthomas on her right forearm, approximately 4 mm each. Treatment with 5-fluorouracil chemotherapy wraps and acitretin 10 mg daily was initiated. At follow-up, the discrete keratoacanthomas had evolved into a 4.0 cm × 3.5 cm crateriform pink tumor with central ulceration consistent with KCM (Fig 1). Histopathology showed SCC with keratoacanthoma features (Fig 2). She underwent radiation therapy to a total dose of 6050 cGy with a combination of megavoltage and orthovoltage photon radiation. She received 5250 cGy in 22 fractions using 6 MV x-ray beam therapy followed by an 800 cGy orthovoltage x-ray boost (100 kilovolt peak [kVp]) in 4 fractions (Figs 3, 4, and 5). The patient was treated 4 days per week because of her hemodialysis schedule. The KCM responded well, with complete resolution; however, during the final week
Conflicts of interest: None. ⁎ Corresponding author. Medical College of Wisconsin, Department of Radiation Oncology, 9200 W Wisconsin Ave, Milwaukee, WI 53226. E-mail address: [email protected] (J. Frank Wilson).
http://dx.doi.org/10.1016/j.prro.2014.10.011 1879-8500/© 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
204
D.P. Lindsay et al
Practical Radiation Oncology: May-June 2015
Figure 3 Setup for radiation therapy. (For color version, see online at www.practicalradonc.org.)
Discussion
of radiation treatment, the patient developed 10 discrete, nontender keratotic nodules within the field of treatment (Fig 6). There were no new nodules anywhere outside the radiation field. Biopsy of a representative nodule confirmed SCC, keratoacanthoma type. Tissue cultures were obtained and were negative. As initially planned, acitretin was increased from 10 mg daily to the goal dose of 20 mg daily. The patient was treated with 5-fluorouracil chemotherapy wraps and intralesional chemotherapy to individual keratoacanthomas on the right arm. Intralesional bleomycin was used initially, followed by 5 weekly treatments with intralesional 5-fluorouracil. All keratoacanthomas responded well, and there were no recurrences at 2-month follow-up (Fig 7).
Keratoacanthomas are a variant of SCC. Although keratoacanthomas usually spontaneously resolve, local destruction, disfiguring scarring, and rare reports of metastasis mandate definitive treatment of all morphological subtypes. Multiple treatment options exist for the treatment of keratoacanthomas, including surgical excision, radiation therapy, oral acitretin, and oral or intralesional chemotherapy. Although radiation therapy is often an effective treatment option, our patient exemplifies the rare occurrence of eruptive keratoacanthomas after radiation treatment. There are few previous reports in the literature of eruptive keratoacanthomas after radiation therapy. Shaw et al 4 described a 51-year-old woman who underwent radiation therapy for an unresectable SCC involving the left maxillary sinus and both ethmoidal sinuses, with extension through both orbital walls. The patient was treated with both megavoltage x-ray and electron beam radiation with a total dose of 6600 cGy. Two weeks after the first radiation
Figure 2 Well-differentiated squamous cell carcinoma with a focal vague crater filled with keratin debris (hematoxylin and eosin, original magnification × 40). (For color version, see online at www.practicalradonc.org.)
Figure 4 Setup for orthovoltage boost with 2 mm aluminum half-value layer shield. (For color version, see online at www. practicalradonc.org.)
Figure 1 Keratoacanthoma centrifugum marginatum on the right forearm. (For color version, see online at www. practicalradonc.org.)
Practical Radiation Oncology: May-June 2015
Eruptive keratoacanthomas after RT
205
Figure 5 Orthovoltage treatment setup. (For color version, see online at www.practicalradonc.org.)
treatment, the patient developed a histologically proven keratoacanthoma on the lower lip. Three weeks after the completion of radiation treatment, she erupted with numerous keratoacanthomas on the central face. She was treated successfully with oral isotretinoin with a starting dose of 2 mg/kg per day. Robertson et al 5 reported a 49-year-old male patient with a history of Ferguson-Smith disease with severe exacerbation followed by radiation treatment for an SCC of the nasal vestibule. The primary SCC resolved after a total radiation dose of 5400 cGy; however, 2 months after the patient completed therapy, he developed multiple
Figure 6 Multiple crateriform keratotic nodules within welldefined erythema corresponding to the field of radiation. Notice the resolution of the primary keratoacanthoma centrifugum marginatum. (For color version, see online at www. practicalradonc.org.)
Figure 7 Resolving keratoacanthomas after oral acitretin, 5fluorouracil chemotherapy wraps, and intralesional chemotherapy. (For color version, see online at www.practicalradonc.org.)
keratoacanthomas within the radiation field. The patient was treated successfully with acitretin 60 mg daily. In a study of families with Ferguson-Smith disease, D’Alessandro et al 6 described 2 patients as experiencing aggravation of their disease by radiation therapy. FergusonSmith, which is also known as multiple self-healing squamous epithelioma, is an autosomal dominant skin cancer disorder characterized by multiple self-healing skin tumors that resemble keratoacanthoma. One patient was treated successfully with surgical excision that required major reconstructive surgery after intralesional interferon alpha/2B therapy failed. The second was treated successfully with acitretin 50 mg daily. The radiation dose used in these patients was not reported. The etiology regarding the effects of radiation on the development of multiple eruptive keratoacanthomas and the overall risk are unknown. Interestingly, in our patient, like those similarly reported, the primary tumor resolved completely before the eruption of multiple keratoacanthomas. Eruptive keratoacanthoma should be considered in patients who develop similar clinical findings after radiation treatment for keratoacanthoma. The decision to use radiation therapy for treatment of patients with a history of multiple keratoacanthomas should be considered with caution because of the unknown risk of eruptive keratoacanthomas within the field of radiation treatment. In this clinical scenario, a reasonable treatment approach for the eruptive keratoacanthomas is acitretin combined with intralesional chemotherapy. This treatment combination has been successful in multiple patients, 3-6 including the present case.
206
D.P. Lindsay et al
References 1. Hodak E, Jones RE, Ackerman AB. Solitary keratoacanthoma is a squamous-cell carcinoma: Three examples with metastases. Am J Dermatopathol. 1993;15:332-342. 2. Bogner PN, Cheney RT, Zeitouni NC. Giant keratoacanthoma: Case report and review of the English literature. Am J Dermatopathol. 2014;36:252-257. 3. Kirby JS, Miller CJ. Intralesional chemotherapy for nonmelanoma skin cancer: A practical review. J Am Acad Dermatol. 2010;63:689-702.
Practical Radiation Oncology: May-June 2015 4. Shaw JC, Storrs FJ, Everts E. Multiple keratoacanthomas after megavoltage radiation therapy. J Am Acad Dermatol. 1990;23(pt 2): 1009-1011. 5. Robertson SJ, Bashir SJ, Pichert G, Robson A, et al. Severe exacerbation of multiple self-healing squamous epithelioma (Ferguson-Smith disease) with radiotherapy, which was successfully treated with acitretin. Clin Exp Dermatol. 2010;35(4):e100-e102. 6. D’Allessandro M, Coats SE, Morley SM, et al. Multiple self-healing squamous epithelioma in different ethnic groups: More than a founder mutation disorder? J Invest Dermatol. 2007;127(10):2336-2344.
