1204 Correspondence
patients with clinically confirmed CS. We did not explore such possible genetic alterations in our study because a different technical approach would be needed. In summary, our study showed that loss of PTEN protein expression is frequently detected in CS-associated trichilemmomas, suggesting that IHC on these benign cutaneous neoplasms may be a useful screening test. These preliminary data also indicate that there is no significant correlation between the loss of PTEN expression as detected by IHC and gene deletion by FISH. Thus, another mechanism must account for PTEN gene inactivation. Further studies of larger sample sizes are needed to define more clearly the prevalence and significance of PTEN status in trichilemmomas. 1
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, PO Box 100275, FL 32610, U.S.A. Departments of 2Dermatology and 3 Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, U.S.A. E-mail: [email protected]
W. SHON1 M.M. WOLZ2 W.R. SUKOV3 C.N. WIELAND2,3 L.E. GIBSON2,3 M.S. PETERS2,3
References 1 Barletta JA, Bellizzi AM, Hornick JL. Immunohistochemical staining of thyroidectomy specimens for PTEN can aid in the identification of patients with Cowden syndrome. Am J Surg Pathol 2011; 35:1505–11. 2 Al-Zaid T, Ditelberg JS, Prieto VG et al. Trichilemmomas show loss of PTEN in Cowden syndrome but only rarely in sporadic tumors. J Cutan Pathol 2012; 39:493–9. 3 Zabetian S, Mehregan D. Cowden syndrome: report of two cases with immunohistochemical analysis for PTEN expression. Am J Dermatopathol 2012; 34:632–4. 4 Jin M, Hampel H, Pilarski R et al. Phosphatase and tensin homolog immunohistochemical staining and clinical criteria for Cowden syndrome in patients with trichilemmoma or associated lesions. Am J Dermatopathol 2013; 35:637–40. 5 Marsh DJ, Coulon V, Lunetta KL et al. Mutation spectrum and genotype–phenotype analyses in Cowden disease and Bannayan– Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. Hum Mol Genet 1998; 7:507–15. Funding sources: none. Conflicts of interest: none declared.
Two cases of pseudolymphoma on the lips DOI: 10.1111/bjd.12837 DEAR EDITOR, Pseudolymphoma is a benign reactive lymphoinfiltrative disorder that usually develops as solitary or multiple British Journal of Dermatology (2014) 170, pp1187–1207
erythematous papules or nodules.1 The face, scalp and neck are the most common sites for pseudolymphoma lesions; the mucosae are rarely involved.1 Here, we report two cases of pseudolymphoma on the lips. Patient 1, a 69-year-old Japanese female, presented with firm, well-demarcated, asymptomatic erythematous papules on the lower lip (Fig. 1a), which started to develop 11 months prior to our examination. She had no causative history, such as drugs, tattooing or tick bites; however, dental metal was observed (Fig. 1a). Histologically, the lesion showed dense infiltrates of mononuclear cells, which formed lymphoid follicle-like structures (Fig. 1b). The infiltrating cells were positive for CD20 and CD10, but mostly negative for CD3, CD30, Bcl2 and herpes simplex virus type I (HSV-I) (Fig. 1b; CD10, CD30, Bcl-2 and HSV-I are not shown). In situ hybridization for Epstein–Barr virus encoding small RNA (EBER) did not show positive cells (not shown). Monoclonal proliferation was excluded by Southern blotting targeting the joining region of the immunoglobulin heavy chain gene using a specific probe (JH; Oncor Inc., Gaithersburg, MD, U.S.A. not shown). Laboratory investigation showed no abnormal findings, such as eosinophils or serum interleukin-2-receptor. We performed patch tests with the following reagents in water or white petrolatum: 2% aluminium chloride, 02% gold chloride, 1% stannic chloride, 2% ferric chloride, 1% palladium chloride, 1% indium chloride, 2% manganese chloride, 2% cobalt chloride, 1% platinum chloride, 2% zinc chloride, 2% silver bromide, 2% chromium sulfate, 5% nickel sulfate, 05% potassium dichromate and 1% copper sulfate (Torii Pharmaceutical Co., Tokyo, Japan). The patient showed mild reaction to platinum chloride and silver bromide at 72 h after application. The eruptions were diagnosed as B-cell pseudolymphoma, and the patient received intralesional injection of triamcinolone acetonide three times per month, which produced partial improvement at 7 months after the initial diagnosis. Patient 2, a 42-year-old Japanese female with a 5-year-history of asymptomatic papules on the lips, presented at our hospital. Initially, the skin eruptions waxed and waned, but for the 4 months prior to the initial visit, they had been persistent (Fig. 2a). Like patient 1, she had no causative history, but dental metal was noticed (Fig. 2a). Histopathology from a lesion showed diffuse infiltrates of mononuclear cells without atypia, which formed lymphoid follicle-like structures (Fig. 2b), and the immunological properties for CD3, CD10, CD20, CD30, Bcl-6 and HSV-I were similar to those of patient 1 (Fig. 2b). EBER in situ hybridization showed no positive cells (not shown). Immunoglobulin j and k light chain-restricted cell populations were not observed, and polymerase chain reaction targeting the joining region of the immunoglobulin heavy chain gene2 excluded monoclonal proliferation (not shown). Laboratory investigation showed increased eosinophils (90%; normal: 0–60%) and positivity for antinuclear antibodies (9 160), but serum interleukin-2-receptor level was within the normal limit. We diagnosed the skin lesions as B-cell pseudolymphoma. The patient did not wish to receive © 2014 British Association of Dermatologists
Correspondence 1205
(a)
(b) Fig 1. Patient 1. (a) Firm, well-demarcated, erythematous papules on the lower lip (arrowheads) and dental metal on her teeth (arrows). (b) Histopathology shows dense infiltrates of mononuclear cells, which form lymphoid follicle-like structures (125 9 magnification). The majority of infiltrating cells are positive for CD20 but CD3-positive cells are scanty.
(a)
(b) Fig 2. Patient 2. (a) Firm, erythematous papules 5–8 mm in diameter on the lips (arrowheads) and dental metal on her teeth (arrows). (b) Histopathology shows dense infiltrates of mononuclear cells, which form lymphoid follicle-like structures (20 9 magnification). The majority of infiltrating cells are positive for CD20 but CD3-positive cells are scanty.
treatment, and the skin lesions showed no distinct changes for the 8 months after the diagnosis. Patch tests performed using the same reagents as for patient 1 showed positive reaction to gold chloride and platinum chloride at 72 h after application (not shown). Pseudolymphoma can develop in mucous membranes, including those in the oral cavity; however, the lips are a rare site for the disease. To our knowledge, only five cases with lip manifestations with detailed clinical and histopathological findings have been described in the English-language literature.3–7 Notably, all seven cases (the previous five cases plus the two patients from the present report) involved lesions on the lower lip, whereas only two of the cases involved both © 2014 British Association of Dermatologists
lips,4 with one of those being our patient 2. Thus, the lower lip is the more common site for pseudolymphoma on the lips. In addition, the clinical manifestations varied from case to case, including nodules,4 papules5 and ulceration.6 Also, reddish papules on the lower lip in the oral cavity have been reported.7 Therefore, histopathological diagnosis is necessary for correct diagnosis of pseudolymphoma on the lip, to differentiate it from malignant lymphoma and other skin diseases which commonly involve the lips, such as granulomatous cheilitis. The pathomechanism of pseudolymphoma on the lip remains uncertain, although it is well known that pseudolymphoma can develop as the result of miscellaneous causative British Journal of Dermatology (2014) 170, pp1187–1207
1206 News and Notices
agents, including drugs, foreign agents and infections.1 Interestingly, a case which developed after tattooing with red mercury-based dyes of the lips has been described.4 Allergic reaction to zinc has been suggested as a causative agent in another case.4 Thus, pseudolymphoma on the lip may develop as a result of reactions to metals. In our cases, allergic reaction to the dental metals may be involved. In summary, pseudolymphoma on the lip is a rare but important differential diagnosis for eruptions on the lips. Department of Dermatology, Hokkaido University Graduate School of Medicine, N15W7 Kita-ku, Sapporo 060-8638, Japan Correspondence: Wataru Nishie. E-mail: [email protected]
N. HAGA W. NISHIE H. HATA T. MIYAUCHI K. MURAMATSU S. KITAMURA R. OSAWA H. SHIMIZU
2 Pablos JL, Carreira PE, Morillas L et al. Clonally expanded lymphocytes in the minor salivary glands of Sj€ogren’s syndrome patients without lymphoproliferative disease. Arthritis Rheum 1994; 37:1441– 4. 3 Del Rio E, Sanchez Yus E, Requena L et al. Oral pseudolymphoma: a report of two cases. J Cutan Pathol 1997; 24:51–5. 4 Komatsu H, Aiba S, Mori S et al. Lymphocytoma cutis involving the lower lip. Contact Dermatitis 1997; 36:167–9. 5 Shin JB, Seo SH, Kim BK et al. Cutaneous T cell pseudolymphoma at the site of a semipermanent lip-liner tattoo. Dermatology 2009; 218:75–8. 6 Itoh S, Masatsugu A, Hinoue A et al. CD30+ pseudolymphoma arising on the lower lip. J Dermatol 2010; 37:685–8. 7 Chen YK, Shen YH, Lin CC, Lin LM. Submucoal lymphoid aggregates of the lower lip in a 10-year-old boy. Br J Oral Maxillofac Surg 2005; 43:185–7. Funding sources: none. Conflicts of interest: none declared.
References 1 Ploysangam T, Breneman DL, Mutasim DF. Cutaneous pseudolymphomas. J Am Acad Dermatol 1998; 38:877–95; quiz 96–7.
News and Notices DOI: 10.1111/bjd.13042
Brish Skin Foundaon Research Funding 2014
The Trustees of the British Skin Foundation are pleased to announce that applications for research funding are now being accepted for the 2014 round of BSF Small Grants. The BSF Small Grant is available to anybody wishing to carry out U.K or R.O.I based research into skin disease. The maximum amount of funds available for each award is £10,000 The project should be a small or pilot project with not more than 50% of the small grant to be used on buying equipment. If part of another project, the small grant is to make-up at least 30% of the total funding The closing date for applications is: Friday 25th April 2014 For full details about the award and downloadable application form and award rules please go to www.britishskin foundation/research
British Journal of Dermatology (2014) 170, pp1187–1207
The 2014 British Skin Foundation major grants which include the Research Award, Studentship, Fellowship and Innovative Project Award will be available from 28th April 2014 If you would like to speak to a member of the BSF team regarding project funding please call the office on 020 7391 6341 or email [email protected] British Skin Foundation 4 Fitzroy Square, London W1T 5HQ T: 020 7391 6341 8th George Rajka International Symposium on Atopic Eczema (ISAD 2014)- 21st-23rd May 2014 Location: East Midlands Conference Centre, Nottingham, UK Cost: Standard delegate fee £250, Trainee delegate fee £100 (20 places available), Developing country delegate fee £100 (10 places available) Meeting Organiser: Prof Hywel Williams Meeting Contact: Dr Carron Layfield, carron.layfield@ nottingham.ac.uk, 0115 8468625 Meeting website and: http://www.nottingham.ac.uk/con ference/fac-mhs/medicine/international-symposium-on-atopicdermatitis/index.aspx On-line registration Invited Speakers: Lisa Beck (US), Mike Cork (UK), Jochen Schmitt (Germany), Alain Taieb (France), Alan Irvine (Eire), Jonathan Silverberg (US), Eric Simpson (US), Robert Boyle (UK), Roberto Takaoka (Brazil), Kim Thomas (UK)
© 2014 British Association of Dermatologists
patients with clinically confirmed CS. We did not explore such possible genetic alterations in our study because a different technical approach would be needed. In summary, our study showed that loss of PTEN protein expression is frequently detected in CS-associated trichilemmomas, suggesting that IHC on these benign cutaneous neoplasms may be a useful screening test. These preliminary data also indicate that there is no significant correlation between the loss of PTEN expression as detected by IHC and gene deletion by FISH. Thus, another mechanism must account for PTEN gene inactivation. Further studies of larger sample sizes are needed to define more clearly the prevalence and significance of PTEN status in trichilemmomas. 1
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, PO Box 100275, FL 32610, U.S.A. Departments of 2Dermatology and 3 Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, U.S.A. E-mail: [email protected]
W. SHON1 M.M. WOLZ2 W.R. SUKOV3 C.N. WIELAND2,3 L.E. GIBSON2,3 M.S. PETERS2,3
References 1 Barletta JA, Bellizzi AM, Hornick JL. Immunohistochemical staining of thyroidectomy specimens for PTEN can aid in the identification of patients with Cowden syndrome. Am J Surg Pathol 2011; 35:1505–11. 2 Al-Zaid T, Ditelberg JS, Prieto VG et al. Trichilemmomas show loss of PTEN in Cowden syndrome but only rarely in sporadic tumors. J Cutan Pathol 2012; 39:493–9. 3 Zabetian S, Mehregan D. Cowden syndrome: report of two cases with immunohistochemical analysis for PTEN expression. Am J Dermatopathol 2012; 34:632–4. 4 Jin M, Hampel H, Pilarski R et al. Phosphatase and tensin homolog immunohistochemical staining and clinical criteria for Cowden syndrome in patients with trichilemmoma or associated lesions. Am J Dermatopathol 2013; 35:637–40. 5 Marsh DJ, Coulon V, Lunetta KL et al. Mutation spectrum and genotype–phenotype analyses in Cowden disease and Bannayan– Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. Hum Mol Genet 1998; 7:507–15. Funding sources: none. Conflicts of interest: none declared.
Two cases of pseudolymphoma on the lips DOI: 10.1111/bjd.12837 DEAR EDITOR, Pseudolymphoma is a benign reactive lymphoinfiltrative disorder that usually develops as solitary or multiple British Journal of Dermatology (2014) 170, pp1187–1207
erythematous papules or nodules.1 The face, scalp and neck are the most common sites for pseudolymphoma lesions; the mucosae are rarely involved.1 Here, we report two cases of pseudolymphoma on the lips. Patient 1, a 69-year-old Japanese female, presented with firm, well-demarcated, asymptomatic erythematous papules on the lower lip (Fig. 1a), which started to develop 11 months prior to our examination. She had no causative history, such as drugs, tattooing or tick bites; however, dental metal was observed (Fig. 1a). Histologically, the lesion showed dense infiltrates of mononuclear cells, which formed lymphoid follicle-like structures (Fig. 1b). The infiltrating cells were positive for CD20 and CD10, but mostly negative for CD3, CD30, Bcl2 and herpes simplex virus type I (HSV-I) (Fig. 1b; CD10, CD30, Bcl-2 and HSV-I are not shown). In situ hybridization for Epstein–Barr virus encoding small RNA (EBER) did not show positive cells (not shown). Monoclonal proliferation was excluded by Southern blotting targeting the joining region of the immunoglobulin heavy chain gene using a specific probe (JH; Oncor Inc., Gaithersburg, MD, U.S.A. not shown). Laboratory investigation showed no abnormal findings, such as eosinophils or serum interleukin-2-receptor. We performed patch tests with the following reagents in water or white petrolatum: 2% aluminium chloride, 02% gold chloride, 1% stannic chloride, 2% ferric chloride, 1% palladium chloride, 1% indium chloride, 2% manganese chloride, 2% cobalt chloride, 1% platinum chloride, 2% zinc chloride, 2% silver bromide, 2% chromium sulfate, 5% nickel sulfate, 05% potassium dichromate and 1% copper sulfate (Torii Pharmaceutical Co., Tokyo, Japan). The patient showed mild reaction to platinum chloride and silver bromide at 72 h after application. The eruptions were diagnosed as B-cell pseudolymphoma, and the patient received intralesional injection of triamcinolone acetonide three times per month, which produced partial improvement at 7 months after the initial diagnosis. Patient 2, a 42-year-old Japanese female with a 5-year-history of asymptomatic papules on the lips, presented at our hospital. Initially, the skin eruptions waxed and waned, but for the 4 months prior to the initial visit, they had been persistent (Fig. 2a). Like patient 1, she had no causative history, but dental metal was noticed (Fig. 2a). Histopathology from a lesion showed diffuse infiltrates of mononuclear cells without atypia, which formed lymphoid follicle-like structures (Fig. 2b), and the immunological properties for CD3, CD10, CD20, CD30, Bcl-6 and HSV-I were similar to those of patient 1 (Fig. 2b). EBER in situ hybridization showed no positive cells (not shown). Immunoglobulin j and k light chain-restricted cell populations were not observed, and polymerase chain reaction targeting the joining region of the immunoglobulin heavy chain gene2 excluded monoclonal proliferation (not shown). Laboratory investigation showed increased eosinophils (90%; normal: 0–60%) and positivity for antinuclear antibodies (9 160), but serum interleukin-2-receptor level was within the normal limit. We diagnosed the skin lesions as B-cell pseudolymphoma. The patient did not wish to receive © 2014 British Association of Dermatologists
Correspondence 1205
(a)
(b) Fig 1. Patient 1. (a) Firm, well-demarcated, erythematous papules on the lower lip (arrowheads) and dental metal on her teeth (arrows). (b) Histopathology shows dense infiltrates of mononuclear cells, which form lymphoid follicle-like structures (125 9 magnification). The majority of infiltrating cells are positive for CD20 but CD3-positive cells are scanty.
(a)
(b) Fig 2. Patient 2. (a) Firm, erythematous papules 5–8 mm in diameter on the lips (arrowheads) and dental metal on her teeth (arrows). (b) Histopathology shows dense infiltrates of mononuclear cells, which form lymphoid follicle-like structures (20 9 magnification). The majority of infiltrating cells are positive for CD20 but CD3-positive cells are scanty.
treatment, and the skin lesions showed no distinct changes for the 8 months after the diagnosis. Patch tests performed using the same reagents as for patient 1 showed positive reaction to gold chloride and platinum chloride at 72 h after application (not shown). Pseudolymphoma can develop in mucous membranes, including those in the oral cavity; however, the lips are a rare site for the disease. To our knowledge, only five cases with lip manifestations with detailed clinical and histopathological findings have been described in the English-language literature.3–7 Notably, all seven cases (the previous five cases plus the two patients from the present report) involved lesions on the lower lip, whereas only two of the cases involved both © 2014 British Association of Dermatologists
lips,4 with one of those being our patient 2. Thus, the lower lip is the more common site for pseudolymphoma on the lips. In addition, the clinical manifestations varied from case to case, including nodules,4 papules5 and ulceration.6 Also, reddish papules on the lower lip in the oral cavity have been reported.7 Therefore, histopathological diagnosis is necessary for correct diagnosis of pseudolymphoma on the lip, to differentiate it from malignant lymphoma and other skin diseases which commonly involve the lips, such as granulomatous cheilitis. The pathomechanism of pseudolymphoma on the lip remains uncertain, although it is well known that pseudolymphoma can develop as the result of miscellaneous causative British Journal of Dermatology (2014) 170, pp1187–1207
1206 News and Notices
agents, including drugs, foreign agents and infections.1 Interestingly, a case which developed after tattooing with red mercury-based dyes of the lips has been described.4 Allergic reaction to zinc has been suggested as a causative agent in another case.4 Thus, pseudolymphoma on the lip may develop as a result of reactions to metals. In our cases, allergic reaction to the dental metals may be involved. In summary, pseudolymphoma on the lip is a rare but important differential diagnosis for eruptions on the lips. Department of Dermatology, Hokkaido University Graduate School of Medicine, N15W7 Kita-ku, Sapporo 060-8638, Japan Correspondence: Wataru Nishie. E-mail: [email protected]
N. HAGA W. NISHIE H. HATA T. MIYAUCHI K. MURAMATSU S. KITAMURA R. OSAWA H. SHIMIZU
2 Pablos JL, Carreira PE, Morillas L et al. Clonally expanded lymphocytes in the minor salivary glands of Sj€ogren’s syndrome patients without lymphoproliferative disease. Arthritis Rheum 1994; 37:1441– 4. 3 Del Rio E, Sanchez Yus E, Requena L et al. Oral pseudolymphoma: a report of two cases. J Cutan Pathol 1997; 24:51–5. 4 Komatsu H, Aiba S, Mori S et al. Lymphocytoma cutis involving the lower lip. Contact Dermatitis 1997; 36:167–9. 5 Shin JB, Seo SH, Kim BK et al. Cutaneous T cell pseudolymphoma at the site of a semipermanent lip-liner tattoo. Dermatology 2009; 218:75–8. 6 Itoh S, Masatsugu A, Hinoue A et al. CD30+ pseudolymphoma arising on the lower lip. J Dermatol 2010; 37:685–8. 7 Chen YK, Shen YH, Lin CC, Lin LM. Submucoal lymphoid aggregates of the lower lip in a 10-year-old boy. Br J Oral Maxillofac Surg 2005; 43:185–7. Funding sources: none. Conflicts of interest: none declared.
References 1 Ploysangam T, Breneman DL, Mutasim DF. Cutaneous pseudolymphomas. J Am Acad Dermatol 1998; 38:877–95; quiz 96–7.
News and Notices DOI: 10.1111/bjd.13042
Brish Skin Foundaon Research Funding 2014
The Trustees of the British Skin Foundation are pleased to announce that applications for research funding are now being accepted for the 2014 round of BSF Small Grants. The BSF Small Grant is available to anybody wishing to carry out U.K or R.O.I based research into skin disease. The maximum amount of funds available for each award is £10,000 The project should be a small or pilot project with not more than 50% of the small grant to be used on buying equipment. If part of another project, the small grant is to make-up at least 30% of the total funding The closing date for applications is: Friday 25th April 2014 For full details about the award and downloadable application form and award rules please go to www.britishskin foundation/research
British Journal of Dermatology (2014) 170, pp1187–1207
The 2014 British Skin Foundation major grants which include the Research Award, Studentship, Fellowship and Innovative Project Award will be available from 28th April 2014 If you would like to speak to a member of the BSF team regarding project funding please call the office on 020 7391 6341 or email [email protected] British Skin Foundation 4 Fitzroy Square, London W1T 5HQ T: 020 7391 6341 8th George Rajka International Symposium on Atopic Eczema (ISAD 2014)- 21st-23rd May 2014 Location: East Midlands Conference Centre, Nottingham, UK Cost: Standard delegate fee £250, Trainee delegate fee £100 (20 places available), Developing country delegate fee £100 (10 places available) Meeting Organiser: Prof Hywel Williams Meeting Contact: Dr Carron Layfield, carron.layfield@ nottingham.ac.uk, 0115 8468625 Meeting website and: http://www.nottingham.ac.uk/con ference/fac-mhs/medicine/international-symposium-on-atopicdermatitis/index.aspx On-line registration Invited Speakers: Lisa Beck (US), Mike Cork (UK), Jochen Schmitt (Germany), Alain Taieb (France), Alan Irvine (Eire), Jonathan Silverberg (US), Eric Simpson (US), Robert Boyle (UK), Roberto Takaoka (Brazil), Kim Thomas (UK)
© 2014 British Association of Dermatologists
