Letters to the Editor
Basal cell carcinoma with an epidermal collarette: A case report and review of published work Dear Editor, A 48-year-old Japanese woman visited our hospital for a tumor on her right thigh in 2013. She noticed it 3 years prior; however, the time when it began to enlarge was unclear. Physical examination showed a well-demarcated dark-brown nodule measuring 5 mm in diameter (Fig. 1a). Dermoscopic features included multiple blue–gray globules and white collarette (Fig. 1b). The lesion was excised with 5mm margin. Histopathologically, the nodular tumor was located in the papillary dermis, and the tumor nest consisted of basaloid cells. Elongated rete ridges infolded from both peripheral sides along with the nests, which corresponded to the epidermal collarette (Fig. 1c). The central part of the collarette below the tumor nests was likely to be a telogen hair follicle (Fig. 1d). Immunohistochemical staining was performed using AE1/AE3, cytokeratin (CK)1, CK6, CD17, CK20 and Ki-67. All parts of the lesion were positive for AE1/AE3 but negative for CK20. Most parts of the epidermal collarette besides the central part were CK1 positive (Fig. 1e). Only the central part was CK6 and CD17 positive (Fig. 1f). The Ki-67 staining of tumor cells entailed a proliferative index of 28.9% (Fig. 1g).
Although small collarette formations may not be so rare in basal cell carcinoma (BCC), only three cases of BCC with an epidermal collarette have been reported.1–3 The first case was reported in 1982, whose details were not described.1 The second case was a 67-year-old Japanese woman with a 6-mm nodule on her eyelid that enlarged within 2 months.2 The third case was an 89-year-old Japanese man with a 10-mm nodule on his left dorsal foot that he noticed 2 years prior.3 Immunohistochemical evaluation of CK expression was not performed in these cases. The origin of the epidermal collarette in BCC has not been established. Jacoby and Ackerman proposed that it was composed of adnexal epithelium rather than epidermis.1 The study suggested that expansively growing BCC pressed against the eccrine glands and ducts and hair follicles, which led to the development of the epidermal collarette from these adnexal structures. On the other hand, Adachi et al.2 proposed that the epidermal collarette was formed by the adnexal epithelium and epidermis. CK1 is expressed in suprabasal epidermal keratinocytes, while both CK6 and CK17 are expressed in sweat glands, lower hair follicles and outer root sheaths.4 Our immunohistochemical and histopathological findings suggest that
(a)
(b)
(c)
(d)
(e)
(f)
(g)
Figure 1. (a) Clinical presentation. A dome-shaped, dark-brown nodule measuring 5 mm in diameter was observed. (b) Dermoscopic findings of the nodule showed multiple blue–gray globules, short fine superficial telangiectasia, reddish homogeneous areas and white collarette. (c–d) Histopathological findings of the tumor. (c) The tumor nest was located in the papillary dermis surrounded by an epidermal collarette (hematoxylin–eosin [HE], original magnification 910). (d) Central part of the collarette below the center of tumor nests showed germinative proliferation (HE, 9200). (e–g) Immunohistochemical staining of epidermal collarette. (e) The majority besides the central part was positive for cytokeratin (CK)1 (940). (f) Central part was positive for CK17 (940). (g) Immunohistochemical staining of tumor cells for Ki-67 (9200).
Correspondence: Noriki Fujimoto, M.D., Ph.D., Department of Dermatology, Shiga University of Medical Science, Setatsukinowacho, Otsu, Shiga 520-2192, Japan. Email: [email protected]
546
© 2015 Japanese Dermatological Association
Letters to the Editor
the epidermal collarette is derived from both adnexal epithelium and epidermis. Furthermore, the mechanism of formation of the epidermal collarette in BCC is unclear. It is well known that epidermal collarette is observed in pyogenic granuloma, which develops over weeks.4 The rapid growth may be one reason. As for BCC, Adachi et al.2 suggested that rapid growth caused an epidermal collarette. The proliferative index of Ki-67 in 51 cases of BCC was reported to range 1–61% and with mean of 12.3%.5 Although rapid growth was not obvious clinically, a higher proliferative index of Ki-67 was observed in our case, which suggests that rapid growth is one of the significant factors for the formation of the epidermal collarette in BCC.
ACKNOWLEDGMENT: Ms Yuko analysis.
Tsukamoto
for
her
The authors would like to thank help with immunohistochemical
CONFLICT OF INTEREST:
The authors have no conflict of
Shinichiro HONDA, Noriki FUJIMOTO, Toshihiro TANAKA Department of Dermatology, Shiga University of Medical Science, Otsu, Shiga, Japan doi: 10.1111/1346-8138.12823
REFERENCES 1 Jacoby RA, Ackerman AB. Is the so-called epidermal collarette formed by epidermal or adnexal epithelium? Am J Dermatopathol 1982; 4(2): 117–124. 2 Adachi K, Miyamoto T, Yoshida Y, Yamamoto O. Basal cell carcinoma with an epidermal collarette. J Dermatol 2007; 34: 844–845. 3 Kiyohara T, Ido T, Hatta N, Kawami K, Kumakiri M. Basal cell carcinoma with an epidermal collarette and ductal differentiation on the dorsal foot. J Dermatol 2012; 39: 1031–1032. 4 Lin RL, Janniger CK. Pyogenic granuloma. Cutis 2004; 74: 229–233. 5 Kramer E, Herman O, Frand J, Leibou L, Schreiber L, Vaknine H. Ki67 as a biologic marker of basal cell carcinoma: a retrospective study. Isr Med Assoc J 2014; 16: 229–232.
interest to declare.
Eruptive melanocytic nevi with satellite lesions following insulin treatment in a girl with type 1 diabetes mellitus Dear Editor, The remarkable feature of eruptive melanocytic nevi (EMN) is the simultaneous and abrupt development of large crops of melanocytic nevi on the skin.1 EMN have been reported after organ transplantation, and immunosuppression has been suggested to favor melanocyte proliferation.2 Herein, we report the case of a 12-year-old girl who presented with EMN following insulin injections. The patient had been diagnosed with type 1 diabetes mellitus (DM) and consequently injecting insulin for 6 months. Except the DM, her general medical condition was good. One month prior to presentation, she noted the sudden development of multiple, small, hyperpigmented papules on her back and arm. On examination, there were multiple, variously sized, brownish papules and plaques with satellite small papules on her back and right arm (Fig. 1a,b). Skin biopsies were performed on the largest plaque and one satellite papule. Histopathological findings revealed compound and intradermal nests of nevus cells, respectively (Fig. 1c,d). To date, she has wanted to remain under observation and there have been no more newly occurring nevi. We presumed that these EMN might have been associated with daily s.c. injections of insulin through some hormonal pathways. According to the published works, EMN have been associated with certain bullous dermatoses and compromised immune
status, such as in AIDS, chemotherapy and after organ transplantation.1,2 It is possible that in patients who are genetically predisposed, the impairment of an intact immune system may permit the rapid proliferation of melanocytes, particularly in children and adolescents, in whom the melanocytic activity is physiologically increased.1 In addition, some case reports described EMN occurring after melanotan injection.3 Melanotan is an unlicensed melanotropic peptide and also known to induce penile erections and increase sexual desire.3,4 It is thought that melanotan induces the EMN by mimicking the actions of the melanocortin a-melanocyte-stimulating hormone (a-MSH) on the MC1 receptors of melanocytes leading to increased expression of eumelanin.3,4 Benoit et al.5 reported that hypothalamic neurons expressing insulin receptors were found to coexpress the melanocortin precursor molecule pro-opiomelanocortin (POMC), and administration of insulin into the third cerebral ventricle of fasted rats increased expression of POMC mRNA. POMC is the source of several important biologically active substances including aMSH. Therefore, in this current report, we suggest that s.c. insulin injections may trigger the occurrence of EMN, particularly in adolescents. Insulin injection has some adverse effects, including hypoglycemia, headaches, cutaneous reactions at the site of the injection (redness, swelling, itching or rash), lipodystrophy, allergic reaction and general body swelling. However, to the best our knowledge, EMN occurring after the s.c. injection of insulin
Correspondence: Kyung Eun Jung, M.D., Department of Dermatology, Eulji University School of Medicine, Eulji University Hospital, 95 Dunsanseo-ro, Seo-gu, Daejeon 302-799, Korea. Email: [email protected]
© 2015 Japanese Dermatological Association
547
Basal cell carcinoma with an epidermal collarette: A case report and review of published work Dear Editor, A 48-year-old Japanese woman visited our hospital for a tumor on her right thigh in 2013. She noticed it 3 years prior; however, the time when it began to enlarge was unclear. Physical examination showed a well-demarcated dark-brown nodule measuring 5 mm in diameter (Fig. 1a). Dermoscopic features included multiple blue–gray globules and white collarette (Fig. 1b). The lesion was excised with 5mm margin. Histopathologically, the nodular tumor was located in the papillary dermis, and the tumor nest consisted of basaloid cells. Elongated rete ridges infolded from both peripheral sides along with the nests, which corresponded to the epidermal collarette (Fig. 1c). The central part of the collarette below the tumor nests was likely to be a telogen hair follicle (Fig. 1d). Immunohistochemical staining was performed using AE1/AE3, cytokeratin (CK)1, CK6, CD17, CK20 and Ki-67. All parts of the lesion were positive for AE1/AE3 but negative for CK20. Most parts of the epidermal collarette besides the central part were CK1 positive (Fig. 1e). Only the central part was CK6 and CD17 positive (Fig. 1f). The Ki-67 staining of tumor cells entailed a proliferative index of 28.9% (Fig. 1g).
Although small collarette formations may not be so rare in basal cell carcinoma (BCC), only three cases of BCC with an epidermal collarette have been reported.1–3 The first case was reported in 1982, whose details were not described.1 The second case was a 67-year-old Japanese woman with a 6-mm nodule on her eyelid that enlarged within 2 months.2 The third case was an 89-year-old Japanese man with a 10-mm nodule on his left dorsal foot that he noticed 2 years prior.3 Immunohistochemical evaluation of CK expression was not performed in these cases. The origin of the epidermal collarette in BCC has not been established. Jacoby and Ackerman proposed that it was composed of adnexal epithelium rather than epidermis.1 The study suggested that expansively growing BCC pressed against the eccrine glands and ducts and hair follicles, which led to the development of the epidermal collarette from these adnexal structures. On the other hand, Adachi et al.2 proposed that the epidermal collarette was formed by the adnexal epithelium and epidermis. CK1 is expressed in suprabasal epidermal keratinocytes, while both CK6 and CK17 are expressed in sweat glands, lower hair follicles and outer root sheaths.4 Our immunohistochemical and histopathological findings suggest that
(a)
(b)
(c)
(d)
(e)
(f)
(g)
Figure 1. (a) Clinical presentation. A dome-shaped, dark-brown nodule measuring 5 mm in diameter was observed. (b) Dermoscopic findings of the nodule showed multiple blue–gray globules, short fine superficial telangiectasia, reddish homogeneous areas and white collarette. (c–d) Histopathological findings of the tumor. (c) The tumor nest was located in the papillary dermis surrounded by an epidermal collarette (hematoxylin–eosin [HE], original magnification 910). (d) Central part of the collarette below the center of tumor nests showed germinative proliferation (HE, 9200). (e–g) Immunohistochemical staining of epidermal collarette. (e) The majority besides the central part was positive for cytokeratin (CK)1 (940). (f) Central part was positive for CK17 (940). (g) Immunohistochemical staining of tumor cells for Ki-67 (9200).
Correspondence: Noriki Fujimoto, M.D., Ph.D., Department of Dermatology, Shiga University of Medical Science, Setatsukinowacho, Otsu, Shiga 520-2192, Japan. Email: [email protected]
546
© 2015 Japanese Dermatological Association
Letters to the Editor
the epidermal collarette is derived from both adnexal epithelium and epidermis. Furthermore, the mechanism of formation of the epidermal collarette in BCC is unclear. It is well known that epidermal collarette is observed in pyogenic granuloma, which develops over weeks.4 The rapid growth may be one reason. As for BCC, Adachi et al.2 suggested that rapid growth caused an epidermal collarette. The proliferative index of Ki-67 in 51 cases of BCC was reported to range 1–61% and with mean of 12.3%.5 Although rapid growth was not obvious clinically, a higher proliferative index of Ki-67 was observed in our case, which suggests that rapid growth is one of the significant factors for the formation of the epidermal collarette in BCC.
ACKNOWLEDGMENT: Ms Yuko analysis.
Tsukamoto
for
her
The authors would like to thank help with immunohistochemical
CONFLICT OF INTEREST:
The authors have no conflict of
Shinichiro HONDA, Noriki FUJIMOTO, Toshihiro TANAKA Department of Dermatology, Shiga University of Medical Science, Otsu, Shiga, Japan doi: 10.1111/1346-8138.12823
REFERENCES 1 Jacoby RA, Ackerman AB. Is the so-called epidermal collarette formed by epidermal or adnexal epithelium? Am J Dermatopathol 1982; 4(2): 117–124. 2 Adachi K, Miyamoto T, Yoshida Y, Yamamoto O. Basal cell carcinoma with an epidermal collarette. J Dermatol 2007; 34: 844–845. 3 Kiyohara T, Ido T, Hatta N, Kawami K, Kumakiri M. Basal cell carcinoma with an epidermal collarette and ductal differentiation on the dorsal foot. J Dermatol 2012; 39: 1031–1032. 4 Lin RL, Janniger CK. Pyogenic granuloma. Cutis 2004; 74: 229–233. 5 Kramer E, Herman O, Frand J, Leibou L, Schreiber L, Vaknine H. Ki67 as a biologic marker of basal cell carcinoma: a retrospective study. Isr Med Assoc J 2014; 16: 229–232.
interest to declare.
Eruptive melanocytic nevi with satellite lesions following insulin treatment in a girl with type 1 diabetes mellitus Dear Editor, The remarkable feature of eruptive melanocytic nevi (EMN) is the simultaneous and abrupt development of large crops of melanocytic nevi on the skin.1 EMN have been reported after organ transplantation, and immunosuppression has been suggested to favor melanocyte proliferation.2 Herein, we report the case of a 12-year-old girl who presented with EMN following insulin injections. The patient had been diagnosed with type 1 diabetes mellitus (DM) and consequently injecting insulin for 6 months. Except the DM, her general medical condition was good. One month prior to presentation, she noted the sudden development of multiple, small, hyperpigmented papules on her back and arm. On examination, there were multiple, variously sized, brownish papules and plaques with satellite small papules on her back and right arm (Fig. 1a,b). Skin biopsies were performed on the largest plaque and one satellite papule. Histopathological findings revealed compound and intradermal nests of nevus cells, respectively (Fig. 1c,d). To date, she has wanted to remain under observation and there have been no more newly occurring nevi. We presumed that these EMN might have been associated with daily s.c. injections of insulin through some hormonal pathways. According to the published works, EMN have been associated with certain bullous dermatoses and compromised immune
status, such as in AIDS, chemotherapy and after organ transplantation.1,2 It is possible that in patients who are genetically predisposed, the impairment of an intact immune system may permit the rapid proliferation of melanocytes, particularly in children and adolescents, in whom the melanocytic activity is physiologically increased.1 In addition, some case reports described EMN occurring after melanotan injection.3 Melanotan is an unlicensed melanotropic peptide and also known to induce penile erections and increase sexual desire.3,4 It is thought that melanotan induces the EMN by mimicking the actions of the melanocortin a-melanocyte-stimulating hormone (a-MSH) on the MC1 receptors of melanocytes leading to increased expression of eumelanin.3,4 Benoit et al.5 reported that hypothalamic neurons expressing insulin receptors were found to coexpress the melanocortin precursor molecule pro-opiomelanocortin (POMC), and administration of insulin into the third cerebral ventricle of fasted rats increased expression of POMC mRNA. POMC is the source of several important biologically active substances including aMSH. Therefore, in this current report, we suggest that s.c. insulin injections may trigger the occurrence of EMN, particularly in adolescents. Insulin injection has some adverse effects, including hypoglycemia, headaches, cutaneous reactions at the site of the injection (redness, swelling, itching or rash), lipodystrophy, allergic reaction and general body swelling. However, to the best our knowledge, EMN occurring after the s.c. injection of insulin
Correspondence: Kyung Eun Jung, M.D., Department of Dermatology, Eulji University School of Medicine, Eulji University Hospital, 95 Dunsanseo-ro, Seo-gu, Daejeon 302-799, Korea. Email: [email protected]
© 2015 Japanese Dermatological Association
547
