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Neuroendocrine carcinoma of the skin (Merkel cell carcinoma): Report of 3 cases
Multikinase inhibitors and their role in cutaneous malignancies
(Poster reference number 5286)
Sophie Momen, MBBS, Kings College Hospital, London, United Kingdom; Saqib Bashir, MBChB, MD, Kings College Hospital, London, United Kingdom Multi kinase inhibitors are licensed in the treatment of solid malignancies including renal and hepatocellular (HCC) with much interest in their uses to treat other malignancies. Multikinase inhibitors have antiangiogenic and antiproliferative actions acting on tumor cells and vessels to inhibit multiple tyrosine, serine, and threonine kinases. Studies have reported the development of cutaneous malignancies following their use, thus a causative role must be addressed. We present two patients with no previous history of skin cancer, treated with a multikinase inhibitor for HCC. Both developed cutaneous malignancies. Patient 1, a 78-year-old man with Fitzpatrick skin type II and a significant history of sun exposure developed eruptive squamoproliferative nodules on his face and genitals 6 weeks after commencing treatment. An erythematous papule on his scalp represented a well differentiated squamous cell carcinoma (SCC) arising on a background of actinic keratosis (AK), a brown warty lesion on his temple represented a well differentiated SCC, both were surgically excised. An SCC on his right nasal ala with perineural invasion was excised by Mohs micrographic surgery and a full thickness graft applied. Treatment was ceased due to HCC progression, 6 months later all lesions had regressed and nil further noted. Patient 2, a 72-year-old man developed a well differentiated nodular basal cell carcinoma on his right cheek 10 months postinitiation of the same multikinase inhibitor that was surgically excised. A subsequent erythematous scalp lesion was a histologically confirmed AK. He is still on treatment and under surveillance. The question arises: why do multikinase inhibitors cause the regression of some malignancies but potentially encourage cutaneous malignancies? Primarily SCCs and keratoacanthomas are reported in the literature. Inhibition of different Ras isoforms, cyclin D1 overexpression, and inflammatory response activation may have a role. Such mechanisms are distinct to those of immunosuppressive drugs in the development of skin cancers. Patient factors may determine why some develop skin cancers. Both cases developed malignancies on sun exposed sites suggesting that this may be a predisposing factor. Evidently, further studies must be undertaken to establish a more putative link. Meanwhile, oncologists and dermatologists must work together to monitor those receiving such therapies.
Oral itraconazole as adjuvant and cytoreductive treatment of basal cell carcinoma
(Poster reference number 5356)
Javier Montoya, MD, Dermatology Department, Facultad de Medicina, Pontificia Universidad Cat olica de Chile, Santiago, Chile; Montserrat Molg o, MD, Dermatology Department, Facultad de Medicina, Pontificia Universidad Cat olica de Chile, Santiago, Chile; Pablo Uribe, PhD, MD, Dermatology Department, Facultad de Medicina, Pontificia Universidad Cat olica de Chile, Santiago, Chile; Sergio Gonzalez, MD, Pathology Department, Facultad de Medicina, Pontificia Universidad Cat olica de Chile, Santiago, Chile Introduction: Basal cell carcinoma (BCC) is the most common cancer in humans and accounts for 75% of skin cancers. In BCC there is a constitutive activation in the sonic hedgehog (Shh) signaling pathway, due to mutations in patched (PTCH) gene in 67% or smoothened (SMO) in10%. Recently itraconazole, an old triazole antifungal, was reported as a hedgehog pathway inhibitor, by inverse agonist binding to SMO. We present our clinical experience with the use of itraconazole as adjuvant and cytoreductive therapy in basal cell carcinoma. Objective: To evaluate the effect of the use of oral itraconazole as adjuvant and cytoreductive therapy for patients with basal cell carcinoma at any skin location. Methods: Five patients with ulcerative BCC, average age 70.8 years (range, 52-98); 1 patient with multiple superficial BCC, one of them ulcerated, 1 patient with ulcerated nodular BCC on the right leg and 3 patients with ulcerated facial BCC were included. All patients had histopathologically confirmed diagnosis; liver function tests at the beginning, at 4 weeks, and at the end of the trial were performed. Patients received itraconazole orally between 100 and 200 mg daily by 8 weeks with clinical and photographic control on a weekly basis from week 1 through 8. Results: At the second week of treatment all cases showed an average decrease of 30% in tumor diameter, associated with reduction in size of skin ulcers, thickness and improved wound healing. No patient had abnormal liver tests at 8 weeks of treatment. Conclusions: The cytoreductive adjuvant treatment with itraconazole can be considered a safe treatment and could be effective in the treatment of BCC.
Commercial support: None identified.
Commercial support: None identified.
Neuroendocrine carcinoma of the skin (Merkel cell carcinoma): Report of 3 cases
Parallel uncertainty for adjuvant radiotherapy indications in cutaneous squamous cell carcinoma (CSCC) with perineural invasion (PNI) among radiation oncologists and Mohs surgeons
(Poster reference number 5113)
Laia Pastor-Jan e, MD, Dermatology, Hospital Universitari Joan XXIII, Tarragona, Spain; Antoni Ravent os-Estelle, MD, Pathology, Hospital Universitari Joan XXIII, Tarragona, Spain; Joan Garcia-Fontgivell, MD, Pathology, Hospital Universitari Joan XXIII, Tarragona, Spain; Josep Pujol-Montcusı, MD, Dermatology, Hospital Universitari Joan XXIII, Tarragona, Spain; Maria Sim o-Esque, MD, Dermatology, Hospital Universitari Joan XXIII, Tarragona, Spain; Pilar Turegano-Fuentes, MD, Dermatology, Hospital Universitari Joan XXIII, Tarragona, Spain Case reports: We report 3 patients with cutaneous tumors that were excised completely and whose histopathology was diagnostic of neuroendocrine carcinoma. Case 1 (March 2006): A 79-year-old man consulted for an erythematous papule on the left cheek of about 1 cm. To date, he has had no lymph node or visceral metastases. Case 2 (February 2011): An 84-year-old woman with a history of gastric carcinoma presented a tumor on the right frontal area. It was an exophytic mass that bled easily and measured 4 cm. On dermoscopy it had aberrant vessels with corkscrew morphology. In a CT scan of the head and neck, 2 intraparotid lymph nodes were found and cytology confirmed that they were metastases. Case 3 (April 2011). A 73-year-old man with a history of prostate carcinoma consulted for a tumor on the left forearm. It was an erythematous and infiltrated nodule of 2 3 1.5 cm. He is currently awaiting results of the extension study. Discussion: Merkel cell carcinoma is a rare tumor that predominates in the elderly (70 years of age or older). Because of its location in photoexposed areas with actinic damage, clinical differential diagnosis can be squamous cell carcinoma, amelanotic melanoma or atypical fibroxanthoma. Sometimes is reddish-purple, so clinically it may resemble an angiosarcoma or a lymphoma. For its rapid growth, it also may seem a cutaneous metastasis. Our 3 patients had tumors of a 1.5-2 months of evolution and rapid growth. Histologically, all the cases showed an atypical cell proliferation in the dermis, organized in trabeculae or nests and composed of small or intermediate-sized cells, with large nuclei and scanty cytoplasm. Immunohistochemistry showed positivity for cytokeratin AE1-AE3 and 20, chromogranin and synaptophysin and negativity for S-100, Melan-A, cytokeratin 7, and thyroid transcription factor 1. The latter two markers are positive in skin metastases of small cell bronchial carcinoma and therefore help to differentiate primary from metastatic lesions. The aggressiveness of this tumor is higher than melanoma. Lymph node metastasis occurs in 55% cases and visceral metastases in 35% cases and affect liver, bone, lung and skin. Commercial support: None identified.
APRIL 2012
(Poster reference number 5660)
Madhu Shetti, MD, University of Washington Medical Center, Seattle, WA, United States; Chrysalyne Schmults, MD, Dana-Farber Cancer Institute, Boston, MA, United States; Daniel Berg, MD, University of Washington Medical Center, Seattle, WA, United States; Upendra Parvathaneni, MD, University of Washington Medical Center, Seattle, WA, United States Background: Management of cutaneous squamous cell carcinoma (CSSC) with perineural invasion (PNI) remains controversial with no clear data on optimal adjuvant radiotherapy (AR) usage. Respondents to a recent survey of randomly selected, fellowship-trained members of the American College of Mohs Surgery (n ¼ 118) indicated lack of consensus for the usage of AR in this setting. Therefore, we conducted a parallel survey among radiation oncologists (ROs) to determine if agreement exists among Mohs surgeons (MS) and ROs for usage of AR in CSCC with PNI. Methods: We invited all ROs and trainees members of the American Society of Therapeutic Radiology and Oncology via their email address. Respondents completed a survey containing vignettes involving CSSC with microscopic PNI (mPNI) following Mohs micrographic surgery clearance; each case varied by one unique poor prognostic factor (ie, immunosuppression, subcutaneous nerve requiring a third stage for clearance [sPNI], or named nerve PNI [nPNI]). Physicians indicated if AR was appropriate. Consensus was defined as 80% acceptance of AR. Survey questions mirrored the Mohs survey questionnaire. Results: Among respondents (n ¼ 352), 70% have 101 years of experience, and 64% have a special interest in treating H & N cancer; 36%, 38%, 16% and 10% respectively treated 0-3, 3-7, 8-10, and 111 cases of CSSC with PNI yearly. Over 95% of ROs recommend AR for cases of nPNI. In cases of mPNI, mPNI with immunosuppression, and sPNI, there was no consensus among ROs to recommend AR. In the Mohs College survey, over 80% recommend AR for nPNI and opinion was divided for AR in cases of mPNI or sPNI. Conclusions: Our data suggests a remarkable consistency between Mohs surgeons and ROs in the indications for AR in cases of CSCC with PNI. MS and ROs would recommend AR for nPNI. Furthermore, both groups are in agreement regarding the lack of consensus for usage of AR in mPNI and sPNI. Further clinical trials are warranted to establish a clear standard of care. Commercial support: None identified.
J AM ACAD DERMATOL
AB155
(Poster reference number 5286)
Sophie Momen, MBBS, Kings College Hospital, London, United Kingdom; Saqib Bashir, MBChB, MD, Kings College Hospital, London, United Kingdom Multi kinase inhibitors are licensed in the treatment of solid malignancies including renal and hepatocellular (HCC) with much interest in their uses to treat other malignancies. Multikinase inhibitors have antiangiogenic and antiproliferative actions acting on tumor cells and vessels to inhibit multiple tyrosine, serine, and threonine kinases. Studies have reported the development of cutaneous malignancies following their use, thus a causative role must be addressed. We present two patients with no previous history of skin cancer, treated with a multikinase inhibitor for HCC. Both developed cutaneous malignancies. Patient 1, a 78-year-old man with Fitzpatrick skin type II and a significant history of sun exposure developed eruptive squamoproliferative nodules on his face and genitals 6 weeks after commencing treatment. An erythematous papule on his scalp represented a well differentiated squamous cell carcinoma (SCC) arising on a background of actinic keratosis (AK), a brown warty lesion on his temple represented a well differentiated SCC, both were surgically excised. An SCC on his right nasal ala with perineural invasion was excised by Mohs micrographic surgery and a full thickness graft applied. Treatment was ceased due to HCC progression, 6 months later all lesions had regressed and nil further noted. Patient 2, a 72-year-old man developed a well differentiated nodular basal cell carcinoma on his right cheek 10 months postinitiation of the same multikinase inhibitor that was surgically excised. A subsequent erythematous scalp lesion was a histologically confirmed AK. He is still on treatment and under surveillance. The question arises: why do multikinase inhibitors cause the regression of some malignancies but potentially encourage cutaneous malignancies? Primarily SCCs and keratoacanthomas are reported in the literature. Inhibition of different Ras isoforms, cyclin D1 overexpression, and inflammatory response activation may have a role. Such mechanisms are distinct to those of immunosuppressive drugs in the development of skin cancers. Patient factors may determine why some develop skin cancers. Both cases developed malignancies on sun exposed sites suggesting that this may be a predisposing factor. Evidently, further studies must be undertaken to establish a more putative link. Meanwhile, oncologists and dermatologists must work together to monitor those receiving such therapies.
Oral itraconazole as adjuvant and cytoreductive treatment of basal cell carcinoma
(Poster reference number 5356)
Javier Montoya, MD, Dermatology Department, Facultad de Medicina, Pontificia Universidad Cat olica de Chile, Santiago, Chile; Montserrat Molg o, MD, Dermatology Department, Facultad de Medicina, Pontificia Universidad Cat olica de Chile, Santiago, Chile; Pablo Uribe, PhD, MD, Dermatology Department, Facultad de Medicina, Pontificia Universidad Cat olica de Chile, Santiago, Chile; Sergio Gonzalez, MD, Pathology Department, Facultad de Medicina, Pontificia Universidad Cat olica de Chile, Santiago, Chile Introduction: Basal cell carcinoma (BCC) is the most common cancer in humans and accounts for 75% of skin cancers. In BCC there is a constitutive activation in the sonic hedgehog (Shh) signaling pathway, due to mutations in patched (PTCH) gene in 67% or smoothened (SMO) in10%. Recently itraconazole, an old triazole antifungal, was reported as a hedgehog pathway inhibitor, by inverse agonist binding to SMO. We present our clinical experience with the use of itraconazole as adjuvant and cytoreductive therapy in basal cell carcinoma. Objective: To evaluate the effect of the use of oral itraconazole as adjuvant and cytoreductive therapy for patients with basal cell carcinoma at any skin location. Methods: Five patients with ulcerative BCC, average age 70.8 years (range, 52-98); 1 patient with multiple superficial BCC, one of them ulcerated, 1 patient with ulcerated nodular BCC on the right leg and 3 patients with ulcerated facial BCC were included. All patients had histopathologically confirmed diagnosis; liver function tests at the beginning, at 4 weeks, and at the end of the trial were performed. Patients received itraconazole orally between 100 and 200 mg daily by 8 weeks with clinical and photographic control on a weekly basis from week 1 through 8. Results: At the second week of treatment all cases showed an average decrease of 30% in tumor diameter, associated with reduction in size of skin ulcers, thickness and improved wound healing. No patient had abnormal liver tests at 8 weeks of treatment. Conclusions: The cytoreductive adjuvant treatment with itraconazole can be considered a safe treatment and could be effective in the treatment of BCC.
Commercial support: None identified.
Commercial support: None identified.
Neuroendocrine carcinoma of the skin (Merkel cell carcinoma): Report of 3 cases
Parallel uncertainty for adjuvant radiotherapy indications in cutaneous squamous cell carcinoma (CSCC) with perineural invasion (PNI) among radiation oncologists and Mohs surgeons
(Poster reference number 5113)
Laia Pastor-Jan e, MD, Dermatology, Hospital Universitari Joan XXIII, Tarragona, Spain; Antoni Ravent os-Estelle, MD, Pathology, Hospital Universitari Joan XXIII, Tarragona, Spain; Joan Garcia-Fontgivell, MD, Pathology, Hospital Universitari Joan XXIII, Tarragona, Spain; Josep Pujol-Montcusı, MD, Dermatology, Hospital Universitari Joan XXIII, Tarragona, Spain; Maria Sim o-Esque, MD, Dermatology, Hospital Universitari Joan XXIII, Tarragona, Spain; Pilar Turegano-Fuentes, MD, Dermatology, Hospital Universitari Joan XXIII, Tarragona, Spain Case reports: We report 3 patients with cutaneous tumors that were excised completely and whose histopathology was diagnostic of neuroendocrine carcinoma. Case 1 (March 2006): A 79-year-old man consulted for an erythematous papule on the left cheek of about 1 cm. To date, he has had no lymph node or visceral metastases. Case 2 (February 2011): An 84-year-old woman with a history of gastric carcinoma presented a tumor on the right frontal area. It was an exophytic mass that bled easily and measured 4 cm. On dermoscopy it had aberrant vessels with corkscrew morphology. In a CT scan of the head and neck, 2 intraparotid lymph nodes were found and cytology confirmed that they were metastases. Case 3 (April 2011). A 73-year-old man with a history of prostate carcinoma consulted for a tumor on the left forearm. It was an erythematous and infiltrated nodule of 2 3 1.5 cm. He is currently awaiting results of the extension study. Discussion: Merkel cell carcinoma is a rare tumor that predominates in the elderly (70 years of age or older). Because of its location in photoexposed areas with actinic damage, clinical differential diagnosis can be squamous cell carcinoma, amelanotic melanoma or atypical fibroxanthoma. Sometimes is reddish-purple, so clinically it may resemble an angiosarcoma or a lymphoma. For its rapid growth, it also may seem a cutaneous metastasis. Our 3 patients had tumors of a 1.5-2 months of evolution and rapid growth. Histologically, all the cases showed an atypical cell proliferation in the dermis, organized in trabeculae or nests and composed of small or intermediate-sized cells, with large nuclei and scanty cytoplasm. Immunohistochemistry showed positivity for cytokeratin AE1-AE3 and 20, chromogranin and synaptophysin and negativity for S-100, Melan-A, cytokeratin 7, and thyroid transcription factor 1. The latter two markers are positive in skin metastases of small cell bronchial carcinoma and therefore help to differentiate primary from metastatic lesions. The aggressiveness of this tumor is higher than melanoma. Lymph node metastasis occurs in 55% cases and visceral metastases in 35% cases and affect liver, bone, lung and skin. Commercial support: None identified.
APRIL 2012
(Poster reference number 5660)
Madhu Shetti, MD, University of Washington Medical Center, Seattle, WA, United States; Chrysalyne Schmults, MD, Dana-Farber Cancer Institute, Boston, MA, United States; Daniel Berg, MD, University of Washington Medical Center, Seattle, WA, United States; Upendra Parvathaneni, MD, University of Washington Medical Center, Seattle, WA, United States Background: Management of cutaneous squamous cell carcinoma (CSSC) with perineural invasion (PNI) remains controversial with no clear data on optimal adjuvant radiotherapy (AR) usage. Respondents to a recent survey of randomly selected, fellowship-trained members of the American College of Mohs Surgery (n ¼ 118) indicated lack of consensus for the usage of AR in this setting. Therefore, we conducted a parallel survey among radiation oncologists (ROs) to determine if agreement exists among Mohs surgeons (MS) and ROs for usage of AR in CSCC with PNI. Methods: We invited all ROs and trainees members of the American Society of Therapeutic Radiology and Oncology via their email address. Respondents completed a survey containing vignettes involving CSSC with microscopic PNI (mPNI) following Mohs micrographic surgery clearance; each case varied by one unique poor prognostic factor (ie, immunosuppression, subcutaneous nerve requiring a third stage for clearance [sPNI], or named nerve PNI [nPNI]). Physicians indicated if AR was appropriate. Consensus was defined as 80% acceptance of AR. Survey questions mirrored the Mohs survey questionnaire. Results: Among respondents (n ¼ 352), 70% have 101 years of experience, and 64% have a special interest in treating H & N cancer; 36%, 38%, 16% and 10% respectively treated 0-3, 3-7, 8-10, and 111 cases of CSSC with PNI yearly. Over 95% of ROs recommend AR for cases of nPNI. In cases of mPNI, mPNI with immunosuppression, and sPNI, there was no consensus among ROs to recommend AR. In the Mohs College survey, over 80% recommend AR for nPNI and opinion was divided for AR in cases of mPNI or sPNI. Conclusions: Our data suggests a remarkable consistency between Mohs surgeons and ROs in the indications for AR in cases of CSCC with PNI. MS and ROs would recommend AR for nPNI. Furthermore, both groups are in agreement regarding the lack of consensus for usage of AR in mPNI and sPNI. Further clinical trials are warranted to establish a clear standard of care. Commercial support: None identified.
J AM ACAD DERMATOL
AB155