Leukemia Cutis Mimicking Granulomatous Rosacea at the Onset of Chronic Lymphocytic Leukemia

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"apellidos" => "Rodríguez-Díaz" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731021002817?idApp=UINPBA000044" "url" => "/00017310/0000011300000003/v2_202212210529/S0001731021002817/v2_202212210529/es/main.assets" ] ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "Case and Research Letter" "titulo" => " Leukemia Cutis Mimicking Granulomatous Rosacea at the Onset of Chronic Lymphocytic Leukemia" "tieneTextoCompleto" => true "saludo" => "To the Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "T326" "paginaFinal" => "T328" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "I. Vázquez-Osorio, P. Chamorro-Chamorro, P. Gonzalvo-Rodríguez, E. Rodríguez-Díaz" "autores" => array:4 [ 0 => array:4 [ "nombre" => "I." "apellidos" => "Vázquez-Osorio" "email" => array:1 [ 0 => "rogivaos@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "P." "apellidos" => "Chamorro-Chamorro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "P." "apellidos" => "Gonzalvo-Rodríguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "E." "apellidos" => "Rodríguez-Díaz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Clínico Universitario de Santiago de CompostelaA Coruña, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Universitario de Cabueñes, Gijón, Asturias, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario de Cabueñes, Gijón, Asturias, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Universitario de Cabueñes, Gijón, Asturias, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Leucemia cutis simulando una rosácea granulomatosa: presentación clínica de una leucemia linfoide crónica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1130 "Ancho" => 1507 "Tamanyo" => 439054 ] ] "descripcion" => array:1 [ "en" => "A, Biopsy of a nodular lesion. Dermal lymphocytic infiltrate composed of small lymphocytes with hyperchromatic, rounded nuclei and scarce cytoplasm (hematoxylin–eosin, 20×). B–D, Positive staining for CD20 (B), BCL-2 (C), and PAX-5 (D) of the lymphocytic infiltrate." ] ] ] "textoCompleto" => "Chronic lymphatic leukemia (CLL) is the most common type of leukemia in adults in Europe and North America. It is characterized by enlarged lymph nodes, visceromegaly, and clonal B-cell lymphocytosis in the peripheral blood. Skin involvement can be seen in up to 25% of patients, mainly in the form of nonspecific manifestations such as neoplasias, viral infections, vasculitis, or Sweet syndrome.<a class="elsevierStyleCrossRef" href="#bib0060">1</a> However, leukemia cutis (LC) or infiltration of the skin by leukemic cells is a rare clinical manifestation in CLL and almost always occurs in advanced stages of the disease.<a class="elsevierStyleCrossRefs" href="#bib0060">1,2</a> We report a rare case of LC mimicking granulomatous rosacea at the onset of CLL.A healthy 60-year-old man with a history of erythematotelangiectatic rosacea visited our department with asymptomatic lesions that had appeared a year earlier on both cheeks. Physical examination revealed erythematous papules on congested skin (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A and B). In light of the clinical suspicion of papulopustular rosacea, treatment with oral doxycycline and topical ivermectin was instated. The course was unfavorable and the patient developed multiple firm, erythematous nodules on the cheeks and outer ears (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C and D). Lymph-node examination revealed a mobile, painless, enlarged right submandibular lymph node. The patient did not present B symptoms. A skin biopsy revealed a diffuse dermal lymphocytic infiltrate with no epidermotropism and with a subepidermal Grenz zone. It consisted of small lymphocytes with round hyperchromatic nuclei and scarce cytoplasm (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A). Demodex folliculorum was not identified. The immunohistochemical analysis revealed a predominantly B phenotype (positive for CD5, CD20 CD23, CD43, BCL-2, LEF-1, and PAX5) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B–D). Morphological and immunohistochemical findings were compatible with a skin infiltration due to CLL. Blood tests showed a normal blood count and hypogammaglobulinemia with no monoclonal bands (IgG, 6.21g/L: IgM, 0.13g/L). Serology was negative for HBV, HCV, HIV, EBV, CMV, and Toxoplasma species. A full-body CT scan revealed multiple enlarged lymph nodes in different locations, with no enlarged liver or spleen. The myelogram identified an infiltration of 83% small, mature lymphocytes, indicative of CLL. Flow cytometry analysis of bone marrow showed 50% B cells with an immunophenotype identical to that found in the skin. The 17p13 deletion was not identified in bone marrow.<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>Following the diagnosis Rai stage I and Binet stage B CLL, the patient underwent 6 cycles of chemotherapy with fludarabine, cyclophosphamide, and rituximab, achieving complete remission (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>A and B). The patient has not experienced a recurrence. After 2 years of follow-up, the patient has not presented cutaneous or bone-marrow recurrences.<elsevierMultimedia ident="fig0015"></elsevierMultimedia>LC can be observed in between 4% and 20% of patients with CLL.<a class="elsevierStyleCrossRef" href="#bib0070">3</a> Although it tends to occur in advanced stages, LC may be the first manifestation of CLL in up to 16.7% of cases.<a class="elsevierStyleCrossRef" href="#bib0075">4</a> Clinical presentation varies widely and includes papules, plaques, nodules, and erythematous-violaceous tumors located essentially on the head and neck, or generalized.<a class="elsevierStyleCrossRef" href="#bib0060">1</a>Onset of CLL mimicking rosacea is a rare form of presentation, with only 4 cases reported to date, 3 of which were in women.<a class="elsevierStyleCrossRefs" href="#bib0080">5–7</a> Patients with CLL have also been reported who developed a rosacea-like facial cutaneous infiltration years after diagnosis.<a class="elsevierStyleCrossRef" href="#bib0095">8</a> This atypical cutaneous manifestation of CLL is mostly observed in women in the 6th decade of life, which makes the differential diagnosis with rosacea more plausible. This leads to a delay in diagnosis, which may range from months to years, given that patients are treated with topical or systemic antibiotics in the event of clinical suspicion of rosacea.<a class="elsevierStyleCrossRef" href="#bib0085">6</a>The etiology and pathogenesis of this form of presentation of CLL are unknown. The appearance of LC in the same location as prior rosacea lesions may represent Wolf's isotopic response, as occurs in patients with a prior infection by the herpes zoster virus or herpes simplex virus.<a class="elsevierStyleCrossRefs" href="#bib0075">4,9</a> It has also been suggested that chronic stimulation by D. folliculorum may lead to the development of lymphoma, as occurs with Helicobacter pylori and gastric MALT lymphoma.<a class="elsevierStyleCrossRef" href="#bib0105">10</a> The presence of D. folliculorum in the histology study, however, has not been shown in all cases of rosacea-like CLL.<a class="elsevierStyleCrossRefs" href="#bib0085">6–8</a>Specific involvement of the skin by leukemic cells in patients with CLL has not been associated with a worse outcome, provided that there is no systemic progression or signs of transformation to large cell lymphoma (Richter syndrome).<a class="elsevierStyleCrossRefs" href="#bib0060">1,4</a>Treatment in these cases includes nucleoside analogs such as fludarabine and cladribine, alkylating agents such as chlorambucil, cyclophosphamide, or local radiation therapy. The combination of rituximab and systemic corticosteroids has also been shown to be effective, especially in patients with poor tolerance of chemotherapy agents.<a class="elsevierStyleCrossRefs" href="#bib0085">6,7,11</a>Thus, the onset of CLL mimicking rosacea is an extremely rare form of clinical presentation. We must, therefore, include atypical rosacea-like lesions or those that respond poorly to the usual treatments in the forms of clinical presentation of CLL to avoid delayed diagnosis.Conflicts of interestThe authors declare that they have no conflicts of interest." 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C and D, Firm erythematous nodule, with a tendency to coalesce on the cheeks and outer ear." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1130 "Ancho" => 1507 "Tamanyo" => 439054 ] ] "descripcion" => array:1 [ "en" => "A, Biopsy of a nodular lesion. Dermal lymphocytic infiltrate composed of small lymphocytes with hyperchromatic, rounded nuclei and scarce cytoplasm (hematoxylin–eosin, 20×). B–D, Positive staining for CD20 (B), BCL-2 (C), and PAX-5 (D) of the lymphocytic infiltrate." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1041 "Ancho" => 906 "Tamanyo" => 121806 ] ] "descripcion" => array:1 [ "en" => "A and B, Complete clinical remission 2 years after treatment." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Skin lesions in chronic lymphocytic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "E. Robak" 1 => "T. 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Case and Research Letter

Leukemia Cutis Mimicking Granulomatous Rosacea at the Onset of Chronic Lymphocytic Leukemia

Leucemia cutis simulando una rosácea granulomatosa: presentación clínica de una leucemia linfoide crónica

I. Vázquez-Osorioa,

Corresponding author

rogivaos@gmail.com

Corresponding author.

, P. Chamorro-Chamorrob, P. Gonzalvo-Rodríguezc, E. Rodríguez-Díazd

a Servicio de Dermatología, Hospital Clínico Universitario de Santiago de CompostelaA Coruña, Spain

b Servicio de Hematología, Hospital Universitario de Cabueñes, Gijón, Asturias, Spain

c Servicio de Anatomía Patológica, Hospital Universitario de Cabueñes, Gijón, Asturias, Spain

d Servicio de Dermatología, Hospital Universitario de Cabueñes, Gijón, Asturias, Spain

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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A&#44; Biopsy of a nodular lesion&#46; Dermal lymphocytic infiltrate composed of small lymphocytes with hyperchromatic&#44; rounded nuclei and scarce cytoplasm &#40;hematoxylin&#8211;eosin&#44; 20&#215;&#41;&#46; B&#8211;D&#44; Positive staining for CD20 &#40;B&#41;&#44; BCL-2 &#40;C&#41;&#44; and PAX-5 &#40;D&#41; of the lymphocytic infiltrate&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic lymphatic leukemia &#40;CLL&#41; is the most common type of leukemia in adults in Europe and North America&#46; It is characterized by enlarged lymph nodes&#44; visceromegaly&#44; and clonal B-cell lymphocytosis in the peripheral blood&#46; Skin involvement can be seen in up to 25&#37; of patients&#44; mainly in the form of nonspecific manifestations such as neoplasias&#44; viral infections&#44; vasculitis&#44; or Sweet syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> However&#44; leukemia cutis &#40;LC&#41; or infiltration of the skin by leukemic cells is a rare clinical manifestation in CLL and almost always occurs in advanced stages of the disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1&#44;2</span></a> We report a rare case of LC mimicking granulomatous rosacea at the onset of CLL&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">A healthy 60-year-old man with a history of erythematotelangiectatic rosacea visited our department with asymptomatic lesions that had appeared a year earlier on both cheeks&#46; Physical examination revealed erythematous papules on congested skin &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A and B&#41;&#46; In light of the clinical suspicion of papulopustular rosacea&#44; treatment with oral doxycycline and topical ivermectin was instated&#46; The course was unfavorable and the patient developed multiple firm&#44; erythematous nodules on the cheeks and outer ears &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C and D&#41;&#46; Lymph-node examination revealed a mobile&#44; painless&#44; enlarged right submandibular lymph node&#46; The patient did not present B symptoms&#46; A skin biopsy revealed a diffuse dermal lymphocytic infiltrate with no epidermotropism and with a subepidermal Grenz zone&#46; It consisted of small lymphocytes with round hyperchromatic nuclei and scarce cytoplasm &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41;&#46; <span class="elsevierStyleItalic">Demodex folliculorum</span> was not identified&#46; The immunohistochemical analysis revealed a predominantly B phenotype &#40;positive for CD5&#44; CD20 CD23&#44; CD43&#44; BCL-2&#44; LEF-1&#44; and PAX5&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#8211;D&#41;&#46; Morphological and immunohistochemical findings were compatible with a skin infiltration due to CLL&#46; Blood tests showed a normal blood count and hypogammaglobulinemia with no monoclonal bands &#40;IgG&#44; 6&#46;21<span class="elsevierStyleHsp" style=""></span>g&#47;L&#58; IgM&#44; 0&#46;13<span class="elsevierStyleHsp" style=""></span>g&#47;L&#41;&#46; Serology was negative for HBV&#44; HCV&#44; HIV&#44; EBV&#44; CMV&#44; and <span class="elsevierStyleItalic">Toxoplasma</span> species&#46; A full-body CT scan revealed multiple enlarged lymph nodes in different locations&#44; with no enlarged liver or spleen&#46; The myelogram identified an infiltration of 83&#37; small&#44; mature lymphocytes&#44; indicative of CLL&#46; Flow cytometry analysis of bone marrow showed 50&#37; B cells with an immunophenotype identical to that found in the skin&#46; The 17p13 deletion was not identified in bone marrow&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Following the diagnosis Rai stage I and Binet stage B CLL&#44; the patient underwent 6 cycles of chemotherapy with fludarabine&#44; cyclophosphamide&#44; and rituximab&#44; achieving complete remission &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>A and B&#41;&#46; The patient has not experienced a recurrence&#46; After 2 years of follow-up&#44; the patient has not presented cutaneous or bone-marrow recurrences&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">LC can be observed in between 4&#37; and 20&#37; of patients with CLL&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> Although it tends to occur in advanced stages&#44; LC may be the first manifestation of CLL in up to 16&#46;7&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> Clinical presentation varies widely and includes papules&#44; plaques&#44; nodules&#44; and erythematous-violaceous tumors located essentially on the head and neck&#44; or generalized&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Onset of CLL mimicking rosacea is a rare form of presentation&#44; with only 4 cases reported to date&#44; 3 of which were in women&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">5&#8211;7</span></a> Patients with CLL have also been reported who developed a rosacea-like facial cutaneous infiltration years after diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> This atypical cutaneous manifestation of CLL is mostly observed in women in the 6th decade of life&#44; which makes the differential diagnosis with rosacea more plausible&#46; This leads to a delay in diagnosis&#44; which may range from months to years&#44; given that patients are treated with topical or systemic antibiotics in the event of clinical suspicion of rosacea&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The etiology and pathogenesis of this form of presentation of CLL are unknown&#46; The appearance of LC in the same location as prior rosacea lesions may represent Wolf&#39;s isotopic response&#44; as occurs in patients with a prior infection by the herpes zoster virus or herpes simplex virus&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">4&#44;9</span></a> It has also been suggested that chronic stimulation by <span class="elsevierStyleItalic">D&#46; folliculorum</span> may lead to the development of lymphoma&#44; as occurs with <span class="elsevierStyleItalic">Helicobacter pylori</span> and gastric MALT lymphoma&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a> The presence of <span class="elsevierStyleItalic">D&#46; folliculorum</span> in the histology study&#44; however&#44; has not been shown in all cases of rosacea-like CLL&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">6&#8211;8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Specific involvement of the skin by leukemic cells in patients with CLL has not been associated with a worse outcome&#44; provided that there is no systemic progression or signs of transformation to large cell lymphoma &#40;Richter syndrome&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1&#44;4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Treatment in these cases includes nucleoside analogs such as fludarabine and cladribine&#44; alkylating agents such as chlorambucil&#44; cyclophosphamide&#44; or local radiation therapy&#46; The combination of rituximab and systemic corticosteroids has also been shown to be effective&#44; especially in patients with poor tolerance of chemotherapy agents&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">6&#44;7&#44;11</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Thus&#44; the onset of CLL mimicking rosacea is an extremely rare form of clinical presentation&#46; We must&#44; therefore&#44; include atypical rosacea-like lesions or those that respond poorly to the usual treatments in the forms of clinical presentation of CLL to avoid delayed diagnosis&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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Article information

ISSN: 00017310
Original language: English

DOI:10.1016/j.ad.2022.02.004

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Year/Month	Html	Pdf	Total

2024 November	17	13	30
2024 October	153	54	207
2024 September	143	53	196
2024 August	178	81	259
2024 July	141	48	189
2024 June	127	83	210
2024 May	202	49	251
2024 April	137	55	192
2024 March	118	58	176
2024 February	96	42	138
2024 January	110	38	148
2023 December	96	28	124
2023 November	127	34	161
2023 October	148	30	178
2023 September	161	38	199
2023 August	123	21	144
2023 July	138	40	178
2023 June	92	33	125
2023 May	162	32	194
2023 April	130	24	154
2023 March	118	44	162
2023 February	78	26	104
2023 January	94	42	136
2022 December	124	38	162
2022 November	100	55	155
2022 October	159	45	204
2022 September	104	43	147
2022 August	92	45	137
2022 July	114	45	159
2022 June	60	36	96
2022 May	185	62	247
2022 April	92	39	131
2022 March	108	53	161
2022 February	84	60	144

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