Letter to the Editor
http://dx.doi.org/10.5021/ad.2016.28.2.262
A Case of Adult Generalized Cutaneous Langerhans Cell Histiocytosis 1
2
Wei-Guo Sun, Lian-Sheng Zhong , Hao Chen
Department of Dermatology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, 1Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 2Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Nanjing, China
Dear Editor: Langerhans cell histiocytosis (LCH) is a rare disease and generally affects infants and children. Adult-onset form and generalized cutaneous lesions at presentation without extracutaneous involvement are uncommon. We report an unusual case of generalized adult cutaneous LCH without extracutaneous involvement. The patient was an 81-year-old man who complained of rapidly growing eruptions on the perianal area, groins, axillae, face, and ankles. He stated that the lesions had been present for about 3 months—they first appeared on the perianal area, and then extended rapidly to the groins, axillae, face, and ankles. Physical examination revealed disseminated violaceous papules and plaques on the perianal area, groins, axillae, face, and ankles; the lesions on the perianal area and groins were confluent and ulcerated (Fig. 1). He had no weight loss and no palpable lymphadenopathy or organomegaly. The laboratory results, including complete blood count with differential, liver, and renal function tests, were within the normal range. Bone marrow biopsy examination revealed no evidence of tumor involvement. In addition, a whole body positron emission tomography/computed tomography study showed no involvement of any organ. Histopathologic findings of the lesions showed diffused infiltration of large tumor cells in the dermis, and epidermotropism was appreciated. The tumor cells had a moderate amount of eosinophilic cytoplasm and grooved nuclei consistent with Langerhans cells. These cells were mixed with small lymphocytes,
neutrophils, and eosinophils (Fig. 1). The immunohistochemistry staining showed that the tumor cells were diffusely positive for S-100, CD1a, langerin, leukocyte common antigen (LCA), CD4, and CD68, but negative for CD3, CD5, CD20, CD34, CD79a, human melanoma black (HMB)-45, and melan-A (Fig. 2). The Ki-67 proliferating index was approximately 60%. Taken together, these morphological and immunological data were consistent with a cutaneous LCH according to the World Health Organization diagnostic criteria. After diagnosis of LCH, the patient was referred to an oncologist and received chemotherapy. However, the patient died of myocardial infarction 10 days after being diagnosed with the disease. LCH is a clonal proliferative disorder of Langerhans cells, typically seen in infants and children. Occurrences of LCH in the adult population are rare, but even rarer with the disease limited to the skin1. Compared with LCH in infants and children, adult LCH occurs predominantly in bone and presents mainly as single system disease, with a more chronic clinical course and a better prognosis. The clinical presentation of cutaneous LCH in adults is variable. It can present as papules, plaques, or nodules localized to a single anatomic site or in a generalized distribution. Pruritic papules or nodules of cutaneous LCH may appear similar to prurigo nodularis, and other (non-LCH) papules or ulcers of the external genitalia1,2. Sites most frequently involved include the scalp, trunk, flexural and intertriginous areas, glabrous skin, and external genitalia1. Treatment of
Received December 11, 2014, Revised April 4, 2015, Accepted for publication May 7, 2015 Corresponding author: Wei-Guo Sun, Department of Dermatology, Huai’an First People’s Hospital, Nanjing Medical University, 6 Beijing West Road, Huaiyin District, Huai’an 223300, China. Tel: 86-13770494557, Fax: 86-0517-84922412, E-mail: [email protected] This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology
262 Ann Dermatol
Letter to the Editor
Fig. 1. (A∼C) Multiple, erythematous, rust-colored papules and plaques with erosions distributed on the perianal area, groins, and axillae; (D∼F) multiple, erythematous macules and papules on the face and ankle.
Fig. 2. (A) Under low-power microscopic examination, the lesion shows diffused infiltration of tumor cells in the dermis (H&E, ×25). (B) The lesion shows infiltration of large tumor cells in the dermis, and epidermotropism was appreciated (H&E, ×100). (C) The tumor cells have a moderate amount of eosinophilic cytoplasm and grooved nuclei consistent with Langerhans cells (H&E, ×400). Immunohistochemical analysis of the lesions shows tumor cells were diffusely positive for: (D) CD1a, (E) langerin, (F) S-100, and (G) CD4. (H) Ki-67 proliferating index is approximately 60% (D∼H: ×100).
cutaneous LCH is controversial. Several therapeutic approaches have been reported in the literature, according to the extent of disease: topical and systemic corticosteroids, topical imiquimod, psoralen plus ultraviolet A (PUVA), thalidomide, interferon-α, vinblastine, and surgery have been used for treating this disease3-5.
REFERENCES 1. Singh A, Prieto VG, Czelusta A, McClain KL, Duvic M. Adult Langerhans cell histiocytosis limited to the skin. Dermatology 2003;207:157-161. 2. Holme SA, Mills CM. Adult primary cutaneous Langerhans' cell histiocytosis mimicking nodular prurigo. Clin Exp
Vol. 28, No. 2, 2016
263
Letter to the Editor
Dermatol 2002;27:250-251.
of pegylated interferon-α. Acta Derm Venereol 2014;94:
3. Aydogan K, Tunali S, Koran Karadogan S, Balaban Adim S,
611-612.
Turan H. Adult-onset Langerhans cell histiocytosis confined
5. Fernandes LB, Guerra JG, Costa MB, Paiva IG, Duran FP,
to the skin. J Eur Acad Dermatol Venereol 2006;20:890-892.
Jacó DN. Langerhans cells histiocytosis with vulvar
4. Furudate S, Fujimura T, Kambayashi Y, Kawano M, Ogasa-
involvement and responding to thalidomide therapy--case
wara K, Tsukada A, et al. Successful treatment of adult onset
report. An Bras Dermatol 2011;86(4 Suppl 1):S78-S81.
Langerhans cell histiocytosis with bi-weekly administration
http://dx.doi.org/10.5021/ad.2016.28.2.264
Mucocutaneous Telangiectasia as a Diagnostic Clue of Hereditary Hemorrhagic Telangiectasia: An Activin Receptor-Like Kinase-1 Mutation in a Korean Patient 1
Jimyung Seo, Howard Chu, Jin Sung Lee , Do Young Kim Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, 1Department of Clinical Genetics, Yonsei University College of Medicine, Seoul, Korea
Dear Editor: Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is an autosomal dominant vascular disorder manifested by variable-sized arteriovenous malformations (AVMs) of the skin, central nervous system, and respiratory, gastrointestinal, and urogenital tracts1,2. A 43-year-old woman visited our dermatology clinic with a 3-year history of increasing numbers of purpuric, punctate, and tiny macules of the lip, oral cavity, and fingers (Fig. 1A∼C). The patient had no history of recurrent epistaxis; however, her mother had recurrent epistaxis and brain AVMs. No other abnormalities were detected in laboratory workups, particularly to detect visceral AVMs, including computed tomography scans of the chest and abdomen, brain magnetic resonance imaging, and gastrointestinal endoscopy. Under clinical suspicion, we per-
formed a mutation analysis for HHT in the patient and her mother. The mutation c.940C＞T (p.His314Tyr) in activin receptor-like kinase-1 (ACVRL1) was confirmed in both the patient and her mother, confirming the diagnosis of HHT (Fig. 1D). Interestingly, this genetic alteration, previously reported in a Western pedigree3, is a novel point mutation in a Korean family. The cutaneous lesions were well improved by pulsed dye laser (Fig. 2). Clinically, HHT is diagnosed by the Curaçao criteria, which include spontaneous and recurrent epistaxis, mucocutaneous telangiectasias, visceral AVMs, and family history of HHT in a first-degree relative1,3. HHT is definitively diagnosed when three of the criteria are satisfied, whereas a suspected diagnosis is given when two of the criteria are met. In molecular diagnosis, mutations are found in approximately 85% of HHT families; most of these cases involve mutations in the endoglin (HHT1) or ACVRL1
Received February 24, 2015, Revised May 7, 2015, Accepted for publication May 7, 2015 Corresponding author: Do Young Kim, Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemoon-gu, Seoul 03722, Korea. Tel: 82-2-2228-2080, Fax: 82-2-393-9157, E-mail: [email protected]. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology
264 Ann Dermatol
http://dx.doi.org/10.5021/ad.2016.28.2.262
A Case of Adult Generalized Cutaneous Langerhans Cell Histiocytosis 1
2
Wei-Guo Sun, Lian-Sheng Zhong , Hao Chen
Department of Dermatology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, 1Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 2Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Nanjing, China
Dear Editor: Langerhans cell histiocytosis (LCH) is a rare disease and generally affects infants and children. Adult-onset form and generalized cutaneous lesions at presentation without extracutaneous involvement are uncommon. We report an unusual case of generalized adult cutaneous LCH without extracutaneous involvement. The patient was an 81-year-old man who complained of rapidly growing eruptions on the perianal area, groins, axillae, face, and ankles. He stated that the lesions had been present for about 3 months—they first appeared on the perianal area, and then extended rapidly to the groins, axillae, face, and ankles. Physical examination revealed disseminated violaceous papules and plaques on the perianal area, groins, axillae, face, and ankles; the lesions on the perianal area and groins were confluent and ulcerated (Fig. 1). He had no weight loss and no palpable lymphadenopathy or organomegaly. The laboratory results, including complete blood count with differential, liver, and renal function tests, were within the normal range. Bone marrow biopsy examination revealed no evidence of tumor involvement. In addition, a whole body positron emission tomography/computed tomography study showed no involvement of any organ. Histopathologic findings of the lesions showed diffused infiltration of large tumor cells in the dermis, and epidermotropism was appreciated. The tumor cells had a moderate amount of eosinophilic cytoplasm and grooved nuclei consistent with Langerhans cells. These cells were mixed with small lymphocytes,
neutrophils, and eosinophils (Fig. 1). The immunohistochemistry staining showed that the tumor cells were diffusely positive for S-100, CD1a, langerin, leukocyte common antigen (LCA), CD4, and CD68, but negative for CD3, CD5, CD20, CD34, CD79a, human melanoma black (HMB)-45, and melan-A (Fig. 2). The Ki-67 proliferating index was approximately 60%. Taken together, these morphological and immunological data were consistent with a cutaneous LCH according to the World Health Organization diagnostic criteria. After diagnosis of LCH, the patient was referred to an oncologist and received chemotherapy. However, the patient died of myocardial infarction 10 days after being diagnosed with the disease. LCH is a clonal proliferative disorder of Langerhans cells, typically seen in infants and children. Occurrences of LCH in the adult population are rare, but even rarer with the disease limited to the skin1. Compared with LCH in infants and children, adult LCH occurs predominantly in bone and presents mainly as single system disease, with a more chronic clinical course and a better prognosis. The clinical presentation of cutaneous LCH in adults is variable. It can present as papules, plaques, or nodules localized to a single anatomic site or in a generalized distribution. Pruritic papules or nodules of cutaneous LCH may appear similar to prurigo nodularis, and other (non-LCH) papules or ulcers of the external genitalia1,2. Sites most frequently involved include the scalp, trunk, flexural and intertriginous areas, glabrous skin, and external genitalia1. Treatment of
Received December 11, 2014, Revised April 4, 2015, Accepted for publication May 7, 2015 Corresponding author: Wei-Guo Sun, Department of Dermatology, Huai’an First People’s Hospital, Nanjing Medical University, 6 Beijing West Road, Huaiyin District, Huai’an 223300, China. Tel: 86-13770494557, Fax: 86-0517-84922412, E-mail: [email protected] This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology
262 Ann Dermatol
Letter to the Editor
Fig. 1. (A∼C) Multiple, erythematous, rust-colored papules and plaques with erosions distributed on the perianal area, groins, and axillae; (D∼F) multiple, erythematous macules and papules on the face and ankle.
Fig. 2. (A) Under low-power microscopic examination, the lesion shows diffused infiltration of tumor cells in the dermis (H&E, ×25). (B) The lesion shows infiltration of large tumor cells in the dermis, and epidermotropism was appreciated (H&E, ×100). (C) The tumor cells have a moderate amount of eosinophilic cytoplasm and grooved nuclei consistent with Langerhans cells (H&E, ×400). Immunohistochemical analysis of the lesions shows tumor cells were diffusely positive for: (D) CD1a, (E) langerin, (F) S-100, and (G) CD4. (H) Ki-67 proliferating index is approximately 60% (D∼H: ×100).
cutaneous LCH is controversial. Several therapeutic approaches have been reported in the literature, according to the extent of disease: topical and systemic corticosteroids, topical imiquimod, psoralen plus ultraviolet A (PUVA), thalidomide, interferon-α, vinblastine, and surgery have been used for treating this disease3-5.
REFERENCES 1. Singh A, Prieto VG, Czelusta A, McClain KL, Duvic M. Adult Langerhans cell histiocytosis limited to the skin. Dermatology 2003;207:157-161. 2. Holme SA, Mills CM. Adult primary cutaneous Langerhans' cell histiocytosis mimicking nodular prurigo. Clin Exp
Vol. 28, No. 2, 2016
263
Letter to the Editor
Dermatol 2002;27:250-251.
of pegylated interferon-α. Acta Derm Venereol 2014;94:
3. Aydogan K, Tunali S, Koran Karadogan S, Balaban Adim S,
611-612.
Turan H. Adult-onset Langerhans cell histiocytosis confined
5. Fernandes LB, Guerra JG, Costa MB, Paiva IG, Duran FP,
to the skin. J Eur Acad Dermatol Venereol 2006;20:890-892.
Jacó DN. Langerhans cells histiocytosis with vulvar
4. Furudate S, Fujimura T, Kambayashi Y, Kawano M, Ogasa-
involvement and responding to thalidomide therapy--case
wara K, Tsukada A, et al. Successful treatment of adult onset
report. An Bras Dermatol 2011;86(4 Suppl 1):S78-S81.
Langerhans cell histiocytosis with bi-weekly administration
http://dx.doi.org/10.5021/ad.2016.28.2.264
Mucocutaneous Telangiectasia as a Diagnostic Clue of Hereditary Hemorrhagic Telangiectasia: An Activin Receptor-Like Kinase-1 Mutation in a Korean Patient 1
Jimyung Seo, Howard Chu, Jin Sung Lee , Do Young Kim Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, 1Department of Clinical Genetics, Yonsei University College of Medicine, Seoul, Korea
Dear Editor: Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is an autosomal dominant vascular disorder manifested by variable-sized arteriovenous malformations (AVMs) of the skin, central nervous system, and respiratory, gastrointestinal, and urogenital tracts1,2. A 43-year-old woman visited our dermatology clinic with a 3-year history of increasing numbers of purpuric, punctate, and tiny macules of the lip, oral cavity, and fingers (Fig. 1A∼C). The patient had no history of recurrent epistaxis; however, her mother had recurrent epistaxis and brain AVMs. No other abnormalities were detected in laboratory workups, particularly to detect visceral AVMs, including computed tomography scans of the chest and abdomen, brain magnetic resonance imaging, and gastrointestinal endoscopy. Under clinical suspicion, we per-
formed a mutation analysis for HHT in the patient and her mother. The mutation c.940C＞T (p.His314Tyr) in activin receptor-like kinase-1 (ACVRL1) was confirmed in both the patient and her mother, confirming the diagnosis of HHT (Fig. 1D). Interestingly, this genetic alteration, previously reported in a Western pedigree3, is a novel point mutation in a Korean family. The cutaneous lesions were well improved by pulsed dye laser (Fig. 2). Clinically, HHT is diagnosed by the Curaçao criteria, which include spontaneous and recurrent epistaxis, mucocutaneous telangiectasias, visceral AVMs, and family history of HHT in a first-degree relative1,3. HHT is definitively diagnosed when three of the criteria are satisfied, whereas a suspected diagnosis is given when two of the criteria are met. In molecular diagnosis, mutations are found in approximately 85% of HHT families; most of these cases involve mutations in the endoglin (HHT1) or ACVRL1
Received February 24, 2015, Revised May 7, 2015, Accepted for publication May 7, 2015 Corresponding author: Do Young Kim, Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemoon-gu, Seoul 03722, Korea. Tel: 82-2-2228-2080, Fax: 82-2-393-9157, E-mail: [email protected]. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology
264 Ann Dermatol
