Correspondence
(a)
(b)
Figure 2 (a) Normal epidermis: in the superficial dermis, highly dilated vessels with eosinophilic amorphous hyaline material can be
seen in the thickened walls, and there is perivascular lymphocytic infiltration (haematoxylin and eosin, original magnification 9100). (b) Dilated vessel in the superficial dermis (periodic-acid–Schiff, original magnification 9 400.
duration. The differential diagnosis includes primary and secondary teleangectasia: generalized essential benign telangiectasia, hereditary hemorrhagic telangiectasia, hereditary benign telangiectasia, telangiectasia eruptiva macularis perstans, and lymphomas. Moreover, a careful history allows CCV to be distinguished from drug-induced benign telangiectasias. CCV is an unusual and possibly under-recognized condition; however, it should be considered in every case of acquired telangiectasia. Further studies are necessary to evaluate whether CCV may be related to systemic disease. F. Bardazzi, A. Virdi, G. Odorici, R. Balestri, S. Infusino, and A. Patrizi Department of Dermatology and Specialised, Experimental and Diagnostic Medicine, Ospedale S. Orsola-Malpighi, Universita di Bologna, Via Massarenti 1, 40138, Bologna,Italy E-mail: [email protected] Conflict of interest: none declared. Accepted for publication 31 August 2013
References 1 Salama S, Rosenthal D. Cutaneous collagenous vasculopathy with generalized telangiectasia: an immunohistochemical and ultrastructural study. J Cutan Pathol 2000; 27: 40–8. 2 Gonz alez Fern andez D, G omez Bernal S et al. Cutaneous collagenous vasculopathy: description of two new cases in elderly women and review of the literature. Dermatology 2012; 225: 1–8. 3 Burdick LM, Losher S, Somach SC, Billings SD. Cutaneous collagenous vasculopathy: a rare cutaneous microangiopathy. Cutan Pathol 2012; 39: 741–6.
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Clinical and Experimental Dermatology (2014) 39, pp216–234
4 Perez A, Wain ME, Robson A et al. Cutaneous collagenous vasculopathy with generalized telangiectasia in two female patients. J Am Acad Dermatol 2010; 63: 882–5. 5 Bernard S, Cawet B, Theate Y et al. Cutaneous collagenous vasculopathy: a rare cause of generalized telangiectasia. Ann Dermatol Venereol 2012; 139: 381–6.
Cutaneous diffuse large B-cell lymphoma, leg type, secondary to testicular diffuse large B-cell lymphoma doi: 10.1111/ced.12255 Diffuse large B-cell lymphoma (DLBCL) is the most common testicular lymphoma in adults. It usually occurs in men older than 60 years, and is an aggressive tumour with intermediate prognosis. Testicular DLBCL can disseminate to diverse extranodal sites, with the skin being a rarely affected site.1,2 An 80-year-old man presented with 1-month history of multiple infiltrated violaceous nodules on his left leg (Fig. 1). He had previously been diagnosed as having a testicular DLBCL, and had been treated with orchidectomy, four courses of chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin and prednisone), prophylactic central nervous system chemotherapy, and radiotherapy to the testis and ipsilateral inguinal lymph nodes, which had resulted in complete response. The cutaneous tumours had first appeared 2 years after resolution. On histological examination of a skin biopsy, a diffuse dermal infiltration of atypical large lymphocytic cells was seen, composed mostly of immunoblasts and centroblasts (Fig. 2). Immunohistochemical markers were positive for
ª 2013 British Association of Dermatologists
Correspondence
(a)
(b)
Figure 1 Erythematoviolaceous nodules on the left leg.
CD20, CD45, Bcl-2 and MUM1, and negative for Bcl-6, CD3 and CD10. The same features were found in sections from the previous testicular lymphoma when these were re-examined. Molecular analysis identified monoclonal rearrangement of the immunoglobulin heavy chain gene by the same clone in testis and skin. A diagnosis of secondary cutaneous involvement of DLBCL-leg type (DLBCL-LT) was established. The patient was treated with three cycles of chemotherapy with rituximab and bendamustine, and posterior local radiotherapy, resulting in partial response. A few weeks later, new violaceous tumours appeared on the patient’s legs and annular erythematous plaques on his left forearm. Skin specimens from both locations confirmed the recurrence of his DLBCL-LT. The patient received local radiotherapy and two cycles of prednisone and cyclophosphamide, but without response, and he is now under terminal palliative care. Primary cutaneous DLBCL-LT (PCDLBCL-LT) is characterized by nodular lesions on one or both legs, but it can also develop at other locations. The histological and immunophenotypical features consist of infiltration by a proliferation of large B cells composed predominantly of immunoblasts and centroblasts, with expression of B-cell markers (CD20, CD19, CD22) and positivity for Bcl-2, MUM-1 and FOXP1. The most common extracutaneous sites of secondary dissemination are the lymph nodes and central nervous system.3,4
ª 2013 British Association of Dermatologists
Figure 2 (a) Diffuse dermal and subcutaneous infiltrate; (b) large
atypical cells with prominent nuclei. Haematoxylin and eosin, original magnification (a) 9 25; (b) 9 630.
Two cases of cutaneous relapse of testicular lymphoma similar to ours are described in the literature. In the first report, a 54-year-old man presented with erythematous plaques on his right buttock and forearm 2 years after treatment of his previous testicular DLBCL.2 NakayamaIchiyama et al. published another case of cutaneous involvement secondary to testicular DLBCL, not otherwise specified. They demonstrated the expression of certain molecules by lymphoma cells such as CCR4, and the positivity for TARC and MDC in the keratinocytes and endothelial cells, proposing that as TARC and MDC are ligands of CCR4, these cytokines could play a main role in the skin involvement by lymphoma cells.5 In addition, two cases have been described of simultaneous appearance of testicular lymphoma and cutaneous DLBCL-LT, with identical clinical, histopathological and immunophenotypical characteristics to PCDLBCL-LT, and there was one case of PCDLBCL-LT with secondary spread to testes.3 We did not find any other reports in which monoclonal rearrangement by the same clone was found in both testicular and cutaneous lesions.
Clinical and Experimental Dermatology (2014) 39, pp216–234
231
Correspondence
In conclusion, we present a case of cutaneous involvement of testicular DLBCL, presenting identical features to PCDLBCL-LT, with monoclonal rearrangement of the immunoglobulin heavy chain gene by the same clone in both sites. We emphasize the need to explore the testes or skin, respectively, when a diagnosis of a PCDLBCL-LT or a testicular DLBCL is made, because of the possibility of the infiltration at these additional locations. A. Pampın,1 E. G omez-de la Fuente,1 R. A. Feltes,1 F. Pinedo,2 J. L. Rodrıguez-Peralto,3 and J. L. L opez-Estebaranz1 Departments of 1Dermatology and 2Pathology, Hospital Universitario Fundacion Alcorcon, Alcorcon, Spain; and 3Department of Pathology, Hospital Universitario Doce de Octubre, Madrid, Spain E-mail: [email protected] Conflict of interest: none declared. Accepted for publication 10 October 2013
References 1 Horne MJ, Adeniran AJ. Primary diffuse large B-cell lymphoma of the testis. Arch Pathol Lab Med 2011; 135: 1363–7. 2 Langar S, Sharma PK, Bhardwaj M et al. Cutaneous relapse of primary testicular non-Hodgkin lymphoma—the first sign of disease dissemination. Indian J Dermatol Venereol Leprol 2010; 76: 576–8. 3 Muniesa C, Pujol RM, Estrach MT et al. Primary cutaneous diffuse large B-cell lymphoma, leg type and secondary cutaneous involvement by testicular B-cell lymphoma share identical clinicopathological and immunophenotypical features. J Am Acad Dermatol 2012; 66: 650–4. 4 Grange F, Beylot-Barry M, Courville P et al. Primary cutaneous diffuse large B-cell lymphoma, leg type. Arch Dermatol 2007; 143: 1144–50. 5 Nakayama-Ichiyama S, Iwaki K, Yokote T et al. Expression of multiple cytokines and CCR4 in primary testicular diffuse large B-cell lymphoma, not otherwise specified, involving the skin. Br J Haematol 2012; 156: 420.
successfully for treating advanced and metastatic renal clear-cell carcinoma and hepatocellular carcinoma. The effect is dose-dependent, and the therapeutic dose is 400 mg twice daily. The signalling pathways and/or receptors inhibited by this new drug are physiologically expressed in the skin and hair follicles, and this explains the fact that cutaneous toxicity is the main adverse event of this drug class.3 It has been estimated that 70–90% of patients receiving sorafenib experienced at least one cutaneous side effect. Hand–foot skin reactions are the most common event, occurring in about 48% of patients, followed by subungual splinter haemorrhage (60%), alopecia (26–27%), stomatitis (26%), erythematous eruption on the trunk (20%), and xerosis cutis and dermatitis-like facial erythema (5%). Results from various studies suggest that the appearance of skin toxicity during treatment may indicate successful antitumor activity.4 We report the case of a 75-year-old white man who presented with four slow-growing lesions on his legs, which had developed over the preceding 3-month period. On physical examination, four indurated, firm, erythematous lesions were seen on the patient’s legs. The lesions had a central slightly oozing cavity, and an appearance similar to that of acne inversa, with formation of cysts and fistulas, although the localization was atypical (Fig 1). The patient had a 1-year history of hepatocellular carcinoma, and at the time of presentation, he had been taking sorafenib 600 mg daily for 6 months. We initially treated the patient with oral amoxicillin/ clavulanic acid and topic fusidic acid, but the lesions persisted. The antibiotic treatment was then changed to ciprofloxacin, and a biopsy was taken from the plaque on the right thigh to exclude cutaneous metastasis. On histopathological examination, the lesion was found to be an infundibular cyst with chronic inflammation and a stromal fibrosis, which had a pattern similar to acne inversa or giant comedo (Fig. 2). Systemic antibiotic therapy was sus-
Acne inversa-like lesions associated with the multi-kinase inhibitor sorafenib doi: 10.1111/ced.12257 Sorafenib is a multikinase-inhibitor, which inhibits the receptor Raf serine/threonine kinases that regulate the ubiquitous Raf/MEK/ERK pathway.1 Dysregulation and overactivation of this pathway is associated with the genesis of solid tumours.2 Sorafenib is also implicated in the inhibition of tumour angiogenesis and progression that is caused by overexpression of tyrosine kinase receptors, leading to aberrant signalling in the vascular endothelial growth factor receptor pathway. Sorafenib has been used
232
Clinical and Experimental Dermatology (2014) 39, pp216–234
Figure 1 Erythematous infiltrated plaque with central cavity on
the right leg.
ª 2013 British Association of Dermatologists
(a)
(b)
Figure 2 (a) Normal epidermis: in the superficial dermis, highly dilated vessels with eosinophilic amorphous hyaline material can be
seen in the thickened walls, and there is perivascular lymphocytic infiltration (haematoxylin and eosin, original magnification 9100). (b) Dilated vessel in the superficial dermis (periodic-acid–Schiff, original magnification 9 400.
duration. The differential diagnosis includes primary and secondary teleangectasia: generalized essential benign telangiectasia, hereditary hemorrhagic telangiectasia, hereditary benign telangiectasia, telangiectasia eruptiva macularis perstans, and lymphomas. Moreover, a careful history allows CCV to be distinguished from drug-induced benign telangiectasias. CCV is an unusual and possibly under-recognized condition; however, it should be considered in every case of acquired telangiectasia. Further studies are necessary to evaluate whether CCV may be related to systemic disease. F. Bardazzi, A. Virdi, G. Odorici, R. Balestri, S. Infusino, and A. Patrizi Department of Dermatology and Specialised, Experimental and Diagnostic Medicine, Ospedale S. Orsola-Malpighi, Universita di Bologna, Via Massarenti 1, 40138, Bologna,Italy E-mail: [email protected] Conflict of interest: none declared. Accepted for publication 31 August 2013
References 1 Salama S, Rosenthal D. Cutaneous collagenous vasculopathy with generalized telangiectasia: an immunohistochemical and ultrastructural study. J Cutan Pathol 2000; 27: 40–8. 2 Gonz alez Fern andez D, G omez Bernal S et al. Cutaneous collagenous vasculopathy: description of two new cases in elderly women and review of the literature. Dermatology 2012; 225: 1–8. 3 Burdick LM, Losher S, Somach SC, Billings SD. Cutaneous collagenous vasculopathy: a rare cutaneous microangiopathy. Cutan Pathol 2012; 39: 741–6.
230
Clinical and Experimental Dermatology (2014) 39, pp216–234
4 Perez A, Wain ME, Robson A et al. Cutaneous collagenous vasculopathy with generalized telangiectasia in two female patients. J Am Acad Dermatol 2010; 63: 882–5. 5 Bernard S, Cawet B, Theate Y et al. Cutaneous collagenous vasculopathy: a rare cause of generalized telangiectasia. Ann Dermatol Venereol 2012; 139: 381–6.
Cutaneous diffuse large B-cell lymphoma, leg type, secondary to testicular diffuse large B-cell lymphoma doi: 10.1111/ced.12255 Diffuse large B-cell lymphoma (DLBCL) is the most common testicular lymphoma in adults. It usually occurs in men older than 60 years, and is an aggressive tumour with intermediate prognosis. Testicular DLBCL can disseminate to diverse extranodal sites, with the skin being a rarely affected site.1,2 An 80-year-old man presented with 1-month history of multiple infiltrated violaceous nodules on his left leg (Fig. 1). He had previously been diagnosed as having a testicular DLBCL, and had been treated with orchidectomy, four courses of chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin and prednisone), prophylactic central nervous system chemotherapy, and radiotherapy to the testis and ipsilateral inguinal lymph nodes, which had resulted in complete response. The cutaneous tumours had first appeared 2 years after resolution. On histological examination of a skin biopsy, a diffuse dermal infiltration of atypical large lymphocytic cells was seen, composed mostly of immunoblasts and centroblasts (Fig. 2). Immunohistochemical markers were positive for
ª 2013 British Association of Dermatologists
Correspondence
(a)
(b)
Figure 1 Erythematoviolaceous nodules on the left leg.
CD20, CD45, Bcl-2 and MUM1, and negative for Bcl-6, CD3 and CD10. The same features were found in sections from the previous testicular lymphoma when these were re-examined. Molecular analysis identified monoclonal rearrangement of the immunoglobulin heavy chain gene by the same clone in testis and skin. A diagnosis of secondary cutaneous involvement of DLBCL-leg type (DLBCL-LT) was established. The patient was treated with three cycles of chemotherapy with rituximab and bendamustine, and posterior local radiotherapy, resulting in partial response. A few weeks later, new violaceous tumours appeared on the patient’s legs and annular erythematous plaques on his left forearm. Skin specimens from both locations confirmed the recurrence of his DLBCL-LT. The patient received local radiotherapy and two cycles of prednisone and cyclophosphamide, but without response, and he is now under terminal palliative care. Primary cutaneous DLBCL-LT (PCDLBCL-LT) is characterized by nodular lesions on one or both legs, but it can also develop at other locations. The histological and immunophenotypical features consist of infiltration by a proliferation of large B cells composed predominantly of immunoblasts and centroblasts, with expression of B-cell markers (CD20, CD19, CD22) and positivity for Bcl-2, MUM-1 and FOXP1. The most common extracutaneous sites of secondary dissemination are the lymph nodes and central nervous system.3,4
ª 2013 British Association of Dermatologists
Figure 2 (a) Diffuse dermal and subcutaneous infiltrate; (b) large
atypical cells with prominent nuclei. Haematoxylin and eosin, original magnification (a) 9 25; (b) 9 630.
Two cases of cutaneous relapse of testicular lymphoma similar to ours are described in the literature. In the first report, a 54-year-old man presented with erythematous plaques on his right buttock and forearm 2 years after treatment of his previous testicular DLBCL.2 NakayamaIchiyama et al. published another case of cutaneous involvement secondary to testicular DLBCL, not otherwise specified. They demonstrated the expression of certain molecules by lymphoma cells such as CCR4, and the positivity for TARC and MDC in the keratinocytes and endothelial cells, proposing that as TARC and MDC are ligands of CCR4, these cytokines could play a main role in the skin involvement by lymphoma cells.5 In addition, two cases have been described of simultaneous appearance of testicular lymphoma and cutaneous DLBCL-LT, with identical clinical, histopathological and immunophenotypical characteristics to PCDLBCL-LT, and there was one case of PCDLBCL-LT with secondary spread to testes.3 We did not find any other reports in which monoclonal rearrangement by the same clone was found in both testicular and cutaneous lesions.
Clinical and Experimental Dermatology (2014) 39, pp216–234
231
Correspondence
In conclusion, we present a case of cutaneous involvement of testicular DLBCL, presenting identical features to PCDLBCL-LT, with monoclonal rearrangement of the immunoglobulin heavy chain gene by the same clone in both sites. We emphasize the need to explore the testes or skin, respectively, when a diagnosis of a PCDLBCL-LT or a testicular DLBCL is made, because of the possibility of the infiltration at these additional locations. A. Pampın,1 E. G omez-de la Fuente,1 R. A. Feltes,1 F. Pinedo,2 J. L. Rodrıguez-Peralto,3 and J. L. L opez-Estebaranz1 Departments of 1Dermatology and 2Pathology, Hospital Universitario Fundacion Alcorcon, Alcorcon, Spain; and 3Department of Pathology, Hospital Universitario Doce de Octubre, Madrid, Spain E-mail: [email protected] Conflict of interest: none declared. Accepted for publication 10 October 2013
References 1 Horne MJ, Adeniran AJ. Primary diffuse large B-cell lymphoma of the testis. Arch Pathol Lab Med 2011; 135: 1363–7. 2 Langar S, Sharma PK, Bhardwaj M et al. Cutaneous relapse of primary testicular non-Hodgkin lymphoma—the first sign of disease dissemination. Indian J Dermatol Venereol Leprol 2010; 76: 576–8. 3 Muniesa C, Pujol RM, Estrach MT et al. Primary cutaneous diffuse large B-cell lymphoma, leg type and secondary cutaneous involvement by testicular B-cell lymphoma share identical clinicopathological and immunophenotypical features. J Am Acad Dermatol 2012; 66: 650–4. 4 Grange F, Beylot-Barry M, Courville P et al. Primary cutaneous diffuse large B-cell lymphoma, leg type. Arch Dermatol 2007; 143: 1144–50. 5 Nakayama-Ichiyama S, Iwaki K, Yokote T et al. Expression of multiple cytokines and CCR4 in primary testicular diffuse large B-cell lymphoma, not otherwise specified, involving the skin. Br J Haematol 2012; 156: 420.
successfully for treating advanced and metastatic renal clear-cell carcinoma and hepatocellular carcinoma. The effect is dose-dependent, and the therapeutic dose is 400 mg twice daily. The signalling pathways and/or receptors inhibited by this new drug are physiologically expressed in the skin and hair follicles, and this explains the fact that cutaneous toxicity is the main adverse event of this drug class.3 It has been estimated that 70–90% of patients receiving sorafenib experienced at least one cutaneous side effect. Hand–foot skin reactions are the most common event, occurring in about 48% of patients, followed by subungual splinter haemorrhage (60%), alopecia (26–27%), stomatitis (26%), erythematous eruption on the trunk (20%), and xerosis cutis and dermatitis-like facial erythema (5%). Results from various studies suggest that the appearance of skin toxicity during treatment may indicate successful antitumor activity.4 We report the case of a 75-year-old white man who presented with four slow-growing lesions on his legs, which had developed over the preceding 3-month period. On physical examination, four indurated, firm, erythematous lesions were seen on the patient’s legs. The lesions had a central slightly oozing cavity, and an appearance similar to that of acne inversa, with formation of cysts and fistulas, although the localization was atypical (Fig 1). The patient had a 1-year history of hepatocellular carcinoma, and at the time of presentation, he had been taking sorafenib 600 mg daily for 6 months. We initially treated the patient with oral amoxicillin/ clavulanic acid and topic fusidic acid, but the lesions persisted. The antibiotic treatment was then changed to ciprofloxacin, and a biopsy was taken from the plaque on the right thigh to exclude cutaneous metastasis. On histopathological examination, the lesion was found to be an infundibular cyst with chronic inflammation and a stromal fibrosis, which had a pattern similar to acne inversa or giant comedo (Fig. 2). Systemic antibiotic therapy was sus-
Acne inversa-like lesions associated with the multi-kinase inhibitor sorafenib doi: 10.1111/ced.12257 Sorafenib is a multikinase-inhibitor, which inhibits the receptor Raf serine/threonine kinases that regulate the ubiquitous Raf/MEK/ERK pathway.1 Dysregulation and overactivation of this pathway is associated with the genesis of solid tumours.2 Sorafenib is also implicated in the inhibition of tumour angiogenesis and progression that is caused by overexpression of tyrosine kinase receptors, leading to aberrant signalling in the vascular endothelial growth factor receptor pathway. Sorafenib has been used
232
Clinical and Experimental Dermatology (2014) 39, pp216–234
Figure 1 Erythematous infiltrated plaque with central cavity on
the right leg.
ª 2013 British Association of Dermatologists
