Letters to the Editor
Human papillomavirus 66-associated subungual squamous cell carcinoma. A 51-year-old Korean female presented with hyperpigmented, verrucous subungual mass and melanonychia with loss of lateral nail plate on her left middle finger for 2 years (Fig. 1a). She was misdiagnosed with verruca vulgaris referred for treatment from her private dermatologic clinic. A skin biopsy showed invasion of dermis and epidermis by atypical keratinocytes which are hyperchromatic, pleomorphic cells with atypical mitosis (Fig. 1b, c). The epidermis showed vacuolated superficial keratinocytes with pyknotic raisin-like nuclei (Fig. 1d). HPV immunohistochemistry showed positive stained infected cells (Fig. 1e). Based on both clinical and histopathological findings, the patient was diagnosed with subungual squamous cell carcinoma. The HPV subtypes, HPV66 and HPV11 were identified by AGBIO Diagnostics HPV DNA genotyping chip (AGBIO Diagnostics, Seoul, Korea). DNA extraction from the tissue specimen and the PCR amplifications of the target region were performed. PCR products were loaded onto HPV DNA Chip with type specific probe, and the scanner read the resulting signal. The HPV genome was localized by in-situ hybridization with the Ventana Inform HPVIII Family 16 probe (Ventana, Tuscon, AZ, USA). In the epidermis, HPV DNA showed typical dot-like positive signals in nuclei (data not shown). Wide excision and split thickness skin grafts were performed. Recurrence has not been observed after wide excision. Of the ungual and periungual HPV-associated SCCs, 27.4% have a history of HPV-associated genital pathology, such as genital warts, cervical or anogenital dysplasia and cancer, or a similar history in a sexual partner.1 According to the carcinogenic potential of the uterine cervix, HPV 66 is a possible carcinogenic subtype (group 2B) and HPV 11 is not classifiable as a carcionogenic subtype (group 3).2 Uncommon HPV subtype 66 as a possible carcinogen is associated with cervical dysplasia and cancer.2 Thus, we performed HPV DNA analyses of our patient’s cervix, but HPV was not detected. In conclusion, high-risk HPV types such as HPV 66 can induce ungual and periungual SCCs.1 High-risk HPV subtypes are
associated with lesions on the cervix and have also been found in oral, ungual and periungual SCC, implying genital-digital and genital-oral viral spread.1 Dermatologists treating patients with ungual and periungual HPV associated SCC should be aware that these may harbor high-risk HPV subtypes with a risk of transmission by skin-to-skin contact or aerosolization of viral particles.1 Aggressive and extensive treatment and close follow-up of HPV-associated ungual and periungual squamous cell carcinoma is necessary due to the high recurrence rate1, the possibility of metastasis1 and high proliferative activity3.
ACKNOWLEDGMENTS: This research was supported by Basic Science Research program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012046972). CONFLICT OF INTEREST:
There are no conflicts of inter-
est in this study.
Jin Hee KANG,1 Hwa young AHN,2 Miri KIM,1 Shin Taek OH,1 Baik Kee CHO,1 Hyun Jeong PARK1 1 Department of Dermatology, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, and 2Hwa Ahn’s Skin Clinic, Seoul, Korea
doi: 10.1111/1346-8138.12680
REFERENCES 1 Riddel C, Rashid R, Thomas V. Ungual and periungual human papillomaviruseassociated squamous cell carcinoma: a review. J Am Acad Dermatol 2011; 64: 1147–1153. 2 Kim NR, Kang M, Lee SP et al. Uncommon and rare human papillomavirus genotypes relating to cervical carcinomas. Korean J Pathol 2014; 48: 43–49. 3 Kreuter A, Gambichler T, Pfister H, Wieland U. Diversity of human papillomavirus types in periungual squamous cell carcinoma. Br J Dermatol 2009; 161: 1262–1269.
Successful treatment of tufted angioma with propranolol Dear Editor A tufted angioma (TA),1 also known as an angioblastoma of Nakagawa, is an uncommon vascular tumor. TA is seen mostly in infancy or early childhood with variable clinical phenotypes. However, there is no consensus in managing TA. We herein report a case of TA that was successfully treated with propranolol. Our patient was a 6-month-old boy who presented with a depressed lesion with a linear subcutaneous induration in his left abdomen (Fig. 1a). Five months prior to
the first visit, the lesion would appear as a widespread purpura, but blood laboratory investigations showed normal levels. The pathological findings showed the aggregation of relatively bloodless and poorly canalized capillaries (Fig. 1b,c). Tumor cells demonstrated positive reactivity for CD34, a-smooth muscle actin and vascular endothelial growth factor (VEGF) (Fig. 1e–g). At 9 months of age, we started to treat the patient with propranolol (1–2 mg/kg per day) under the careful observation of
Correspondence: Yuki Yamamoto, M.D., Ph.D., and Fukumi Furukawa, M.D., Ph.D., Department of Dermatology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, Japan. Emails: [email protected]; [email protected]
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© 2014 Japanese Dermatological Association
Letters to the Editor
(a)
(d)
(b)
(e)
(c)
(f)
(g)
Figure 1. (a) Before treatment, the clinical appearance was compatible with a diagnosis of tufted angioma (TA). (b,c) Histopathological findings showed nests of relatively bloodless tumor cells in the dermis (hematoxylin–eosin [HE], original magnification 9100) composed of bloodless capillaries surrounded by bland oval to slightly spindly tumor cells (HE, 9200). Immunohistochemical studies showed the positivity of (e) CD34, (f) a-smooth muscle actin and (g) vascular endothelial growth factor (9400). (d) After treatment, the TA almost disappeared and the lesion softened.
potential hypotension, sinus bradycardia and hypoglycemia by a pediatric cardiologist. The induration of the lesion almost disappeared over a 1-month period. After 6 months of propranolol treatment, the TA showed a smooth, soft and darkred colored lesion. However, tumor cells were found in the dermis of biopsy specimens. For the next 4 months, we continued the propranolol treatment and the TA almost disappeared and the lesion softened (Fig. 1d). We performed the third biopsy after 10 months of propranolol treatment and found that the tumor cells had disappeared. No complications of propranolol were observed during the treatment. Oral propranolol was reported to be effective in treating complicated infantile hemangiomas (IH) with impressive efficacy.2 Beta-blockers like propranolol lead to a reduced expression of VEGF and thus to an inhibition of angiogenesis.3 Effects of propranolol on growing IH are based on vasoconstriction, inhibition of angiogenesis and induction of apoptosis.3 Propranolol is usually used in young infants for hypertension and congestive heart failure at doses up to 8 mg/kg per day. Many reports of successful treatment of IH show that propranolol of 2 mg/kg per day worked well until the end of the proliferation phase. Complications of propranolol treat-
© 2014 Japanese Dermatological Association
ment in IH reported adverse events such as hypotension, sinus bradycardia and hypoglycemia, but these were not lifethreatening. In the future, we must assess the optimal dose and duration of treatment. As reported by Chiu et al.,4 further studies are required to generate more clinical experience with propranolol in the treatment of TA.
CONFLICT OF INTEREST:
None.
Yuki YAMAMOTO,1 Shinji KOUNAMI,2 Hisako OKUHIRA,1 Yasushi NAKAMURA,3 Fukumi FURUKAWA1 Departments of 1Dermatology, 2Pediatrics, and 3Clinical Laboratory Medicine, Wakayama Medical University, Wakayama, Japan doi: 10.1111/1346-8138.12665
REFERENCES 1 Wilson-Jones E, Orkin M. Tufted angioma (angioblastoma): a benign progressive angioma, not to be confused with Kaposi’s sarcoma or low-grade angiosarcoma. J Am Acad Dermatol 1989; 20: 214–215. 2 Sans V, de la Roque ED, Berge J et al. Propranolol for severe infantile hemangiomas: follow-up report. Pediatrics 2009; 124: 423–431.
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Letters to the Editor
3 Storch CH, Hoeger PH. Propranolol for infantile haemangiomas: insights into the molecular mechanisms of action. Br J Dermatol 2010; 163: 269–274.
4 Chiu YE, Drolet BA, Blei F et al. Variable response to propranolol treatment of kaposiform hemangioendothelioma, tufted angioma, and Kasabach-Merritt phenomenon. Pediatr Blood Cancer 2012; 59: 934–938.
Primary breast carcinoma en cuirasse derived from invasive lobular carcinoma: The first case report Dear Editor, Carcinoma en cuirasse (CEC) preferentially arises in association with the cutaneous involvement of breast carcinomas. A large percentage of cases of breast CECs are secondary (recurrent) lesions following a breast operation, while 0.6– 10% of the cases are primary lesions, i.e., the first manifestation of the breast carcinoma.1 Herein we report an unusual case of primary breast CEC and discuss the importance of E-cadherin immunohistochemistry for their histopathological classification. A 60-year-old Japanese woman with no remarkable medical history visited our hospital complaining of an unusual eruption
(a)
on her right breast that slowly increased in size over 35 years. A physical examination revealed a keloid-like erythematous plaque around the right nipple (Fig. 1a). An MRI scan demonstrated an irregular mass on the right mammary gland directly extending to the overlying skin. No other neoplastic lesions were found by CT screening. The findings of the skin biopsy corresponded histologically to the “Indian file” pattern, which consists of dermal changes with a proliferation of thickened collagen bundles and infiltration of a small number of atypical neoplastic cells with linear arrangement between collagen bundles (Fig. 1b,c). Immunohistochemistry showed that the atypical cells were positive for the estrogen receptor (Fig. 1d) and
(b)
(d)
(c)
(e)
Figure 1. (a) Clinical picture of the eruption. Hard, thickened, irregular-shaped, keloid-like erythematous plaque, 10 9 8 cm in size, was observed around the right nipple. (b, c) Histopathology of the skin biopsy specimen taken from the keloid-like lesion revealed dermal changes marked by proliferation of thickened collagen bundles and infiltration of a small number of atypical neoplastic cells with large nuclei arranged in cords and strands between collagen bundles. (b) Low magnification (HE, 9200). (c) High magnification (HE, 9400). (d, e) Immunohistochemical examination demonstrated that the atypical cells were positive for estrogen receptor (d, 9400) but were negative for E-cadherin (e, 9400).
Correspondence: Yuta Kurashige, MD, PhD, Department of Dermatology, Tokai University School of Medicine, 143 Shimokasuya, Isehara-shi, Kanagawa 259-1193, Japan. Email: [email protected]
1122
© 2014 Japanese Dermatological Association
Human papillomavirus 66-associated subungual squamous cell carcinoma. A 51-year-old Korean female presented with hyperpigmented, verrucous subungual mass and melanonychia with loss of lateral nail plate on her left middle finger for 2 years (Fig. 1a). She was misdiagnosed with verruca vulgaris referred for treatment from her private dermatologic clinic. A skin biopsy showed invasion of dermis and epidermis by atypical keratinocytes which are hyperchromatic, pleomorphic cells with atypical mitosis (Fig. 1b, c). The epidermis showed vacuolated superficial keratinocytes with pyknotic raisin-like nuclei (Fig. 1d). HPV immunohistochemistry showed positive stained infected cells (Fig. 1e). Based on both clinical and histopathological findings, the patient was diagnosed with subungual squamous cell carcinoma. The HPV subtypes, HPV66 and HPV11 were identified by AGBIO Diagnostics HPV DNA genotyping chip (AGBIO Diagnostics, Seoul, Korea). DNA extraction from the tissue specimen and the PCR amplifications of the target region were performed. PCR products were loaded onto HPV DNA Chip with type specific probe, and the scanner read the resulting signal. The HPV genome was localized by in-situ hybridization with the Ventana Inform HPVIII Family 16 probe (Ventana, Tuscon, AZ, USA). In the epidermis, HPV DNA showed typical dot-like positive signals in nuclei (data not shown). Wide excision and split thickness skin grafts were performed. Recurrence has not been observed after wide excision. Of the ungual and periungual HPV-associated SCCs, 27.4% have a history of HPV-associated genital pathology, such as genital warts, cervical or anogenital dysplasia and cancer, or a similar history in a sexual partner.1 According to the carcinogenic potential of the uterine cervix, HPV 66 is a possible carcinogenic subtype (group 2B) and HPV 11 is not classifiable as a carcionogenic subtype (group 3).2 Uncommon HPV subtype 66 as a possible carcinogen is associated with cervical dysplasia and cancer.2 Thus, we performed HPV DNA analyses of our patient’s cervix, but HPV was not detected. In conclusion, high-risk HPV types such as HPV 66 can induce ungual and periungual SCCs.1 High-risk HPV subtypes are
associated with lesions on the cervix and have also been found in oral, ungual and periungual SCC, implying genital-digital and genital-oral viral spread.1 Dermatologists treating patients with ungual and periungual HPV associated SCC should be aware that these may harbor high-risk HPV subtypes with a risk of transmission by skin-to-skin contact or aerosolization of viral particles.1 Aggressive and extensive treatment and close follow-up of HPV-associated ungual and periungual squamous cell carcinoma is necessary due to the high recurrence rate1, the possibility of metastasis1 and high proliferative activity3.
ACKNOWLEDGMENTS: This research was supported by Basic Science Research program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012046972). CONFLICT OF INTEREST:
There are no conflicts of inter-
est in this study.
Jin Hee KANG,1 Hwa young AHN,2 Miri KIM,1 Shin Taek OH,1 Baik Kee CHO,1 Hyun Jeong PARK1 1 Department of Dermatology, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, and 2Hwa Ahn’s Skin Clinic, Seoul, Korea
doi: 10.1111/1346-8138.12680
REFERENCES 1 Riddel C, Rashid R, Thomas V. Ungual and periungual human papillomaviruseassociated squamous cell carcinoma: a review. J Am Acad Dermatol 2011; 64: 1147–1153. 2 Kim NR, Kang M, Lee SP et al. Uncommon and rare human papillomavirus genotypes relating to cervical carcinomas. Korean J Pathol 2014; 48: 43–49. 3 Kreuter A, Gambichler T, Pfister H, Wieland U. Diversity of human papillomavirus types in periungual squamous cell carcinoma. Br J Dermatol 2009; 161: 1262–1269.
Successful treatment of tufted angioma with propranolol Dear Editor A tufted angioma (TA),1 also known as an angioblastoma of Nakagawa, is an uncommon vascular tumor. TA is seen mostly in infancy or early childhood with variable clinical phenotypes. However, there is no consensus in managing TA. We herein report a case of TA that was successfully treated with propranolol. Our patient was a 6-month-old boy who presented with a depressed lesion with a linear subcutaneous induration in his left abdomen (Fig. 1a). Five months prior to
the first visit, the lesion would appear as a widespread purpura, but blood laboratory investigations showed normal levels. The pathological findings showed the aggregation of relatively bloodless and poorly canalized capillaries (Fig. 1b,c). Tumor cells demonstrated positive reactivity for CD34, a-smooth muscle actin and vascular endothelial growth factor (VEGF) (Fig. 1e–g). At 9 months of age, we started to treat the patient with propranolol (1–2 mg/kg per day) under the careful observation of
Correspondence: Yuki Yamamoto, M.D., Ph.D., and Fukumi Furukawa, M.D., Ph.D., Department of Dermatology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, Japan. Emails: [email protected]; [email protected]
1120
© 2014 Japanese Dermatological Association
Letters to the Editor
(a)
(d)
(b)
(e)
(c)
(f)
(g)
Figure 1. (a) Before treatment, the clinical appearance was compatible with a diagnosis of tufted angioma (TA). (b,c) Histopathological findings showed nests of relatively bloodless tumor cells in the dermis (hematoxylin–eosin [HE], original magnification 9100) composed of bloodless capillaries surrounded by bland oval to slightly spindly tumor cells (HE, 9200). Immunohistochemical studies showed the positivity of (e) CD34, (f) a-smooth muscle actin and (g) vascular endothelial growth factor (9400). (d) After treatment, the TA almost disappeared and the lesion softened.
potential hypotension, sinus bradycardia and hypoglycemia by a pediatric cardiologist. The induration of the lesion almost disappeared over a 1-month period. After 6 months of propranolol treatment, the TA showed a smooth, soft and darkred colored lesion. However, tumor cells were found in the dermis of biopsy specimens. For the next 4 months, we continued the propranolol treatment and the TA almost disappeared and the lesion softened (Fig. 1d). We performed the third biopsy after 10 months of propranolol treatment and found that the tumor cells had disappeared. No complications of propranolol were observed during the treatment. Oral propranolol was reported to be effective in treating complicated infantile hemangiomas (IH) with impressive efficacy.2 Beta-blockers like propranolol lead to a reduced expression of VEGF and thus to an inhibition of angiogenesis.3 Effects of propranolol on growing IH are based on vasoconstriction, inhibition of angiogenesis and induction of apoptosis.3 Propranolol is usually used in young infants for hypertension and congestive heart failure at doses up to 8 mg/kg per day. Many reports of successful treatment of IH show that propranolol of 2 mg/kg per day worked well until the end of the proliferation phase. Complications of propranolol treat-
© 2014 Japanese Dermatological Association
ment in IH reported adverse events such as hypotension, sinus bradycardia and hypoglycemia, but these were not lifethreatening. In the future, we must assess the optimal dose and duration of treatment. As reported by Chiu et al.,4 further studies are required to generate more clinical experience with propranolol in the treatment of TA.
CONFLICT OF INTEREST:
None.
Yuki YAMAMOTO,1 Shinji KOUNAMI,2 Hisako OKUHIRA,1 Yasushi NAKAMURA,3 Fukumi FURUKAWA1 Departments of 1Dermatology, 2Pediatrics, and 3Clinical Laboratory Medicine, Wakayama Medical University, Wakayama, Japan doi: 10.1111/1346-8138.12665
REFERENCES 1 Wilson-Jones E, Orkin M. Tufted angioma (angioblastoma): a benign progressive angioma, not to be confused with Kaposi’s sarcoma or low-grade angiosarcoma. J Am Acad Dermatol 1989; 20: 214–215. 2 Sans V, de la Roque ED, Berge J et al. Propranolol for severe infantile hemangiomas: follow-up report. Pediatrics 2009; 124: 423–431.
1121
Letters to the Editor
3 Storch CH, Hoeger PH. Propranolol for infantile haemangiomas: insights into the molecular mechanisms of action. Br J Dermatol 2010; 163: 269–274.
4 Chiu YE, Drolet BA, Blei F et al. Variable response to propranolol treatment of kaposiform hemangioendothelioma, tufted angioma, and Kasabach-Merritt phenomenon. Pediatr Blood Cancer 2012; 59: 934–938.
Primary breast carcinoma en cuirasse derived from invasive lobular carcinoma: The first case report Dear Editor, Carcinoma en cuirasse (CEC) preferentially arises in association with the cutaneous involvement of breast carcinomas. A large percentage of cases of breast CECs are secondary (recurrent) lesions following a breast operation, while 0.6– 10% of the cases are primary lesions, i.e., the first manifestation of the breast carcinoma.1 Herein we report an unusual case of primary breast CEC and discuss the importance of E-cadherin immunohistochemistry for their histopathological classification. A 60-year-old Japanese woman with no remarkable medical history visited our hospital complaining of an unusual eruption
(a)
on her right breast that slowly increased in size over 35 years. A physical examination revealed a keloid-like erythematous plaque around the right nipple (Fig. 1a). An MRI scan demonstrated an irregular mass on the right mammary gland directly extending to the overlying skin. No other neoplastic lesions were found by CT screening. The findings of the skin biopsy corresponded histologically to the “Indian file” pattern, which consists of dermal changes with a proliferation of thickened collagen bundles and infiltration of a small number of atypical neoplastic cells with linear arrangement between collagen bundles (Fig. 1b,c). Immunohistochemistry showed that the atypical cells were positive for the estrogen receptor (Fig. 1d) and
(b)
(d)
(c)
(e)
Figure 1. (a) Clinical picture of the eruption. Hard, thickened, irregular-shaped, keloid-like erythematous plaque, 10 9 8 cm in size, was observed around the right nipple. (b, c) Histopathology of the skin biopsy specimen taken from the keloid-like lesion revealed dermal changes marked by proliferation of thickened collagen bundles and infiltration of a small number of atypical neoplastic cells with large nuclei arranged in cords and strands between collagen bundles. (b) Low magnification (HE, 9200). (c) High magnification (HE, 9400). (d, e) Immunohistochemical examination demonstrated that the atypical cells were positive for estrogen receptor (d, 9400) but were negative for E-cadherin (e, 9400).
Correspondence: Yuta Kurashige, MD, PhD, Department of Dermatology, Tokai University School of Medicine, 143 Shimokasuya, Isehara-shi, Kanagawa 259-1193, Japan. Email: [email protected]
1122
© 2014 Japanese Dermatological Association
