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2012&#44; due to a cutaneous lesion on the right breast related to an insect bite 3 months earlier&#46; The lesion consisted of an itchy erythematous nodule measuring 2<span class="elsevierStyleHsp" style=""></span>cm in diameter with a smooth surface &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Biopsy showed a dense and diffuse infiltrate that occupied the entire thickness of the dermis&#44; composed of small and medium sized cells alongside some eosinophils &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Epidermotropism was scarce&#46; Abundant histiocytes and multinucleated giant cells were also observed&#44; forming granulomatous aggregates &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#44; interspersed with lymphoid proliferation&#46; Immunohistochemistry showed CD3&#43; and CD4&#43; cells that were however negative for CD8 and CD30 &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; Molecular study of the &#955; chain of the T-cell receptor showed monoclonal rearrangement&#44; and so the patient was diagnosed with primary cutaneous granulomatous small-to-medium sized CD4&#43; T-cell lymphoma&#46; An extension study was conducted&#44; including study with lymphoid subpopulations&#44; LDH&#44; &#946;2-microglobulin&#44; and positron emission tomography-computed tomography&#44; with normal results&#46; Surgical resection was proposed&#46; On the day of surgery&#44; 2 months later&#44; the nodule had disappeared to leave a residual erythematous macule &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Excision biopsy of the lesion showed a considerable reduction in lymphoid infiltrate&#44; but this remained positive for CD20&#44; CD3&#44; and CD68&#44; with predominance of CD4 over CD8&#59; the infiltrate was negative for CD30&#46; The same monoclonal pattern persisted&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The patient is still in follow-up in our department and is disease free after 2 years&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Primary cutaneous small-to-medium-sized CD4&#43; T-cell lymphoma is a rare T-cell lymphoid proliferation that usually presents as a single lesion on the head or trunk and whose histology findings coincide with the case described&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#44;3</span></a> Prognosis is good&#44; with 5-year survival of 80&#37;&#44; with good response to chemotherapy or surgery&#46; In aggressive cases&#44; with multiple lesions&#44; polychemotherapy such as CHOP is used&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The association of cutaneous lymphoma and granuloma is rare although well known&#46; The presence of lymphoma and granuloma in biopsy can lead to erroneous diagnosis and enable the disease to progress undetected for months&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In the literature review&#44; this phenomenon occurs most frequently in mycosis fungoides and its clinical variant granulomatous slack skin&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> but there have also been isolated reports in S&#233;zary syndrome&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6&#44;7</span></a> anaplastic CD30&#43; lymphoma&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> panniculitis-type T lymphoma&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> follicle center lymphoma&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> and in 4 cases of primary cutaneous small-to-medium&#8211;sized CD4&#43; T-cell lymphoma&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> A lymphoma is considered granulomatous when the granulomas occupy at least 25&#37; of the infiltrate&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> This finding occurs in 1&#46;8&#37; of all cutaneous lymphomas&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">It is not known whether the granuloma occurs as an immune response of the host to tumor cells or is a result of cytokine release&#44; contributing to better prognosis&#46; Beltraminelli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> went as far as to suggest that small granulomas could be secondary to destruction of skin appendages&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The extent to which this immune reaction could influence the prognosis of lymphoma has also not been established&#46; Granulomatous cutaneous lymphomas normally have a slowly progressive course&#44; although around 50&#37; develop nodal lymphomas with a fatal outcome&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The incongruence between histological findings &#40;pleomorphism&#44; appendage destruction&#44; T-cell monoclonality&#41; and the favorable clinical outcome with a high percentage of remissions seems paradoxic&#46; Histology and immunohistochemistry are&#44; for the time being&#44; not helpful in this case&#46; The monoclonality found in the infiltrate is suggestive of a malign lymphoproliferative process but this finding is not exclusive as reactive inflammatory processes and other processes of unknown significance can also be monoclonal&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> The pattern of PD-1 immuno expression&#44; which we could not determine in our case&#44; may have helped in the diagnosis of primary cutaneous small-to-medium-sized CD4&#43; T-cell lymphoma&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Patients with solitary lesions usually have an indolent course&#46; Aggressive treatments should be avoided and these patients should be managed differently to those with multiple cutaneous lesions&#44; in whom prognosis may not be favorable&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">In summary&#44; we describe a case of granulomatous primary cutaneous small-to-medium&#8211;sized CD4&#43; T-cell lymphoma with partial self-resolution&#46; The lymphoma has remained in complete remission after surgical excision&#46; Although the presence of granulomas in the histology may hinder diagnosis of the primary tumor&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> and enable its progression&#44; in other cases it may be a true host-versus-tumor reaction and favor self-resolution&#46;</p></span>"
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Case and Research Letters
Primary cutaneous small-to-medium-sized CD4+ T-cell lymphoma with a granulomatous component
Linfoma cutáneo primario T CD4+ de célula pequeña/mediana, granulomatoso
M.R. García de la Fuentea,
Autor para correspondencia
mrgarcia_dlf@hotmail.com

Corresponding author.
, F. Vilardell-Villellasb, R.M. Martí-Labordaa, J.M. Casanova-Seumaa
a Servicio de Dermatología, Hospital Universitario Arnau de Vilanova, Lérida, Spain
b Servicio de Anatomía Patológica, Hospital Universitario Arnau de Vilanova, Lérida, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We describe a patient with primary cutaneous small-to-medium&#8211;sized CD4&#43; T-cell lymphoma&#44; according to the most recent World Health Organization &#40;WHO&#41; classification of cutaneous lymphomas&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">This lymphoma&#44; previously known as primary cutaneous small-to-medium-sized pleomorphic CD4&#43; T-cell lymphoma&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> has a low incidence and good prognosis&#46; The interest in the case presented in this report derives from a substantial granulomatous component in the clinical-pathological study and the self-healing nature of the lesion&#46; We discuss the possibility of a relationship between these 2 characteristics&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The patient was a 32-year-old woman with no clinical history of relevance who attended the clinic in December&#44; 2012&#44; due to a cutaneous lesion on the right breast related to an insect bite 3 months earlier&#46; The lesion consisted of an itchy erythematous nodule measuring 2<span class="elsevierStyleHsp" style=""></span>cm in diameter with a smooth surface &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Biopsy showed a dense and diffuse infiltrate that occupied the entire thickness of the dermis&#44; composed of small and medium sized cells alongside some eosinophils &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Epidermotropism was scarce&#46; Abundant histiocytes and multinucleated giant cells were also observed&#44; forming granulomatous aggregates &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#44; interspersed with lymphoid proliferation&#46; Immunohistochemistry showed CD3&#43; and CD4&#43; cells that were however negative for CD8 and CD30 &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; Molecular study of the &#955; chain of the T-cell receptor showed monoclonal rearrangement&#44; and so the patient was diagnosed with primary cutaneous granulomatous small-to-medium sized CD4&#43; T-cell lymphoma&#46; An extension study was conducted&#44; including study with lymphoid subpopulations&#44; LDH&#44; &#946;2-microglobulin&#44; and positron emission tomography-computed tomography&#44; with normal results&#46; Surgical resection was proposed&#46; On the day of surgery&#44; 2 months later&#44; the nodule had disappeared to leave a residual erythematous macule &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Excision biopsy of the lesion showed a considerable reduction in lymphoid infiltrate&#44; but this remained positive for CD20&#44; CD3&#44; and CD68&#44; with predominance of CD4 over CD8&#59; the infiltrate was negative for CD30&#46; The same monoclonal pattern persisted&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The patient is still in follow-up in our department and is disease free after 2 years&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Primary cutaneous small-to-medium-sized CD4&#43; T-cell lymphoma is a rare T-cell lymphoid proliferation that usually presents as a single lesion on the head or trunk and whose histology findings coincide with the case described&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#44;3</span></a> Prognosis is good&#44; with 5-year survival of 80&#37;&#44; with good response to chemotherapy or surgery&#46; In aggressive cases&#44; with multiple lesions&#44; polychemotherapy such as CHOP is used&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The association of cutaneous lymphoma and granuloma is rare although well known&#46; The presence of lymphoma and granuloma in biopsy can lead to erroneous diagnosis and enable the disease to progress undetected for months&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In the literature review&#44; this phenomenon occurs most frequently in mycosis fungoides and its clinical variant granulomatous slack skin&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> but there have also been isolated reports in S&#233;zary syndrome&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6&#44;7</span></a> anaplastic CD30&#43; lymphoma&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> panniculitis-type T lymphoma&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> follicle center lymphoma&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> and in 4 cases of primary cutaneous small-to-medium&#8211;sized CD4&#43; T-cell lymphoma&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> A lymphoma is considered granulomatous when the granulomas occupy at least 25&#37; of the infiltrate&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> This finding occurs in 1&#46;8&#37; of all cutaneous lymphomas&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">It is not known whether the granuloma occurs as an immune response of the host to tumor cells or is a result of cytokine release&#44; contributing to better prognosis&#46; Beltraminelli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> went as far as to suggest that small granulomas could be secondary to destruction of skin appendages&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The extent to which this immune reaction could influence the prognosis of lymphoma has also not been established&#46; Granulomatous cutaneous lymphomas normally have a slowly progressive course&#44; although around 50&#37; develop nodal lymphomas with a fatal outcome&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The incongruence between histological findings &#40;pleomorphism&#44; appendage destruction&#44; T-cell monoclonality&#41; and the favorable clinical outcome with a high percentage of remissions seems paradoxic&#46; Histology and immunohistochemistry are&#44; for the time being&#44; not helpful in this case&#46; The monoclonality found in the infiltrate is suggestive of a malign lymphoproliferative process but this finding is not exclusive as reactive inflammatory processes and other processes of unknown significance can also be monoclonal&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> The pattern of PD-1 immuno expression&#44; which we could not determine in our case&#44; may have helped in the diagnosis of primary cutaneous small-to-medium-sized CD4&#43; T-cell lymphoma&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Patients with solitary lesions usually have an indolent course&#46; Aggressive treatments should be avoided and these patients should be managed differently to those with multiple cutaneous lesions&#44; in whom prognosis may not be favorable&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">In summary&#44; we describe a case of granulomatous primary cutaneous small-to-medium&#8211;sized CD4&#43; T-cell lymphoma with partial self-resolution&#46; The lymphoma has remained in complete remission after surgical excision&#46; Although the presence of granulomas in the histology may hinder diagnosis of the primary tumor&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> and enable its progression&#44; in other cases it may be a true host-versus-tumor reaction and favor self-resolution&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Garc&#237;a de la Fuente MR&#44; Vilardell-Villellas F&#44; Mart&#237;-Laborda RM&#44; Casanova-Seuma JM&#46; Linfoma cut&#225;neo primario T CD4&#43; de c&#233;lula peque&#241;a&#47;mediana&#44; granulomatoso&#46; Actas Dermosifiliogr&#46; 2016&#59;107&#58;89&#8211;91&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical images of the lesion&#46; A&#44; At the first visit&#46; B&#44; 2 months later&#44; with self-resolution&#46; Histological appearance of the biopsies corresponding to the clinical images immediately above&#44; with partial reduction of the tumor infiltrate in the second of them&#46; C&#44; Hematoxylin-eosin &#40;H-E&#41;&#44; x40&#46; D&#44; H-E&#44; x400&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Histological appearance&#46; Of note is the presence of numerous multinucleated gigant cells &#40;H-E&#44; x200&#41;&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">In the immunohistochemical study&#44; of note was positivity for CD3 and CD4 in the upper images and negativity for CD8 and CD30 in the lower ones&#46; The limited staining for CD8 corresponds to accompanying cellularity and not tumoral cellularity&#46;</p>"
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