ORIGINAL
ARTICLE
Atypical clinicopathologic presentation of primary cutaneous diffuse large B-cell lymphoma, leg type Cesare Massone, MD, Regina Fink-Puches, MD, Ingrid Wolf, MD, Iris Zalaudek, MD, and Lorenzo Cerroni, MD Graz, Austria Background: Primary cutaneous diffuse large B-cell lymphoma, leg type (cDLBCL-LT) is a well-defined entity of cutaneous B-cell lymphoma affecting predominantly elderly patients, mostly women. The typical clinical presentation is characterized by solitary or multiple, rapidly growing plaques or tumors on 1 leg (rarely both legs). Objective: We sought to describe a new clinical variant of cDLBCL-LT that deviates from the conventional one. Methods: Clinical, histopathologic, phenotypical, and molecular features of 3 cases of cDLBCL-LT presenting with patches or thin plaques were reviewed (all were women, aged 60, 62, and 87 years; lesions were located on the leg in all patients). Results: These patients presented with patches or thin plaques that represented the first manifestation of cDLBCL-LT. All 3 patients reported a history of long-standing lesions (present for 6, 9, and 18 months, respectively). Histology revealed moderately dense, perivascular infiltrates of small lymphocytes admixed with variable numbers of large cells that were CD201, Bcl-21, and MUM-11. Limitations: There were only a small number of cases. Conclusions: We reported an unusual clinical presentation of cDLBCL-LT that deviates from the conventional one and that represents a formidable diagnostic challenge. Biopsy specimens of unusual patches/thin plaques or annular lesions should be obtained from the legs of adult patients if the lesions do not respond to conventional treatment. ( J Am Acad Dermatol http://dx.doi.org/10.1016/j.jaad.2015.02.1134.) Key words: annular erythema; clinical presentation; cutaneous B-cell lymphoma; primary cutaneous diffuse large B-cell lymphoma; leg type.
P
rimary cutaneous diffuse large B-cell lymphoma, leg type (cDLBCL-LT) is a welldefined entity of cutaneous B-cell lymphoma (CBCL) affecting predominantly elderly patients, mostly women.1-3 In most cases, the clinical presentation is characterized by solitary or localized, sometimes ulcerated plaques or tumors located on 1 or both legs. In rare cases, large, ulcerated lesions may be clinically difficult to differentiate from venous leg ulcers.3-5 Another rare clinical presentation with a migratory lesion has been described in 1 patient.6 From the Dermatopathology Research Unit, Department of Dermatology, Medical University of Graz. Funding sources: None. Conflicts of interest: None declared. Accepted for publication February 24, 2015. Correspondence to: Lorenzo Cerroni, MD, Department of Dermatology, Medical University of Graz, Auenbruggerplatz 8, A-8036 Graz, Austria. E-mail: [email protected].
Abbreviations used: CBCL: cDLBCL-LT: PCR:
cutaneous B-cell lymphoma cutaneous diffuse large B-cell lymphoma, leg type polymerase chain reaction
We have recently observed 3 patients with cDLBCL-LT with an atypical presentation characterized by variably large erythematous, infiltrated Published online March 27, 2015. 0190-9622/$36.00 Ó 2015 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2015.02.1134
1
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2 Massone et al
n 2015
radiotherapy, achieving complete remission. At last follow-up in December 2014, she was free of lesions. Patient 2. A 62-year-old woman presented to our department in June 2007 with a 9-month history of a slowly enlarging, asymptomatic erythematous lesion REPORT OF 3 CASES on her right ankle. The clinical examination revealed Patient 1. A 60-year-old woman presented a 10- 3 7-cm annular, slightly infiltrated erythemain January 2014 with an asymptomatic 10- 3 8-cm tous patch (Fig 3). Her medical annular patch with eryhistory was relevant only for thematous, well-defined CAPSULE SUMMARY hypothyroidism. She was borders and apparently taking levothyroxine, pentoxnormal skin in the center Primary cutaneous diffuse large B-cell ifylline, and acetylsalicylic (Fig 1). The lesion had lymphoma, leg type is characterized acid. A 4-mm biopsy specimen appeared 6 months earlier. clinically by solitary or localized, was obtained that revealed a The patient was living in sometimes ulcerated plaques or tumors moderately dense perivascua region endemic for located on 1 or both legs. lar and interstitial infiltrate in Borrelia, and in December We report 3 cases of cutaneous diffuse the papillary and reticular 2013 her general practilarge B-cell lymphoma, leg type with an dermis. The infiltrate was tioner treated her with atypical presentation characterized by composed by small lymphodoxycycline (200 mg/day) variably large erythematous, partly cytes admixed with large, for 3 weeks under a preannular patches or thin plaques in the atypical cell that were positive sumptive diagnosis of absence of tumors. for CD20, Bcl-2, Bcl-6 erythema chronicum mi(focally), and MUM-1 and grans, but without any Biopsy specimens of unusual patches/ negative for CD3, CD4, CD56, improvement. A clinical thin plaques or annular lesions on the CD30, and TdT (Fig 4). Small examination did not reveal legs of elderly patients should be reactive lymphocytes were any other lesion. Her obtained if the lesions do not respond to also present. In situ hybridizamedical history revealed conventional treatment. tion for EBER-1 was negative. Hashimoto thyroiditis with The proliferation rate detected hypothyroidism, osteopewith the Ki-67 antibody was [80%. PCR for Borrelia nia, arterial hypertension, and hypercholesterolemia burgdorferi was negative. A diagnosis of cDLBCL-LT treated with levothyroxine, cholecalciferol, was made. Hemocrome and cytofluorometry of bisoprolol, and simvastatin. Routine laboratory peripheral blood, CT scans of the thorax and investigations were within normal limits. A 4-mm abdomen, and bone marrow biopsy specimens did biopsy specimen was obtained that revealed a not reveal pathologic alterations. The patient was normal epidermis, dilated vessels in the dermis, treated with systemic chemotherapy (R-CHOP) and a perivascular infiltrate composed of large followed by autologous stem cell transplantation lymphocytes that were positive for CD20, PAX-5, with complete remission. In January 2009, she Bcl-2, MUM-1, and focally Bcl-6 and negative for developed a cutaneous relapse on her right leg CD3, CD4, CD56, CD30, and TdT (Fig 2). Small followed by rapid systemic dissemination. The reactive lymphocytes were also present. In situ patient died in February 2009. hybridization for EpsteineBarr virus (EBER-1) was Patient 3. An 87-year-old woman was referred to negative. The proliferation rate detected with the our department in April 2013 because of an Ki-67 antibody was [80%. A polymerase chain asymptomatic, erythematous thin plaque on her left reaction (PCR) analysis for Borrelia burgdorferi leg (Fig 5). The lesion appeared 18 months earlier, and was negative. A diagnosis of early stage cDLBCL-LT she reported slow enlargement of the lesion. was made. Complete staging investigations inclusive The clinical examination revealed an 8- 3 7.5-cm of hemocrome of peripheral blood, computed erythematous thin plaque on the left leg. She was tomography (CT) scans of the thorax and abdomen, taking bisoprolol and spironolactone for blood a bone marrow biopsy specimen, and cytofluoromhypertension, simvastatin for hypercholesteroetry of peripheral blood did not reveal lymphoma lemia, phenprocoumon for atrial fibrillation, and infiltration. Molecular analyses did not reveal a cholecalciferol for osteoporosis. Two 4-mm punch 14;18 translocation. In March 2014, the patient was biopsies were obtained, revealing similar features. treated with systemic chemotherapy (cyclophosphaHistology was characterized by a superficial and mide, hydroxydaunorubicin, vincristine, prednisodeep perivascular infiltrate composed of small lone, and rituximab [R-CHOP]) followed by local patches/thin plaques in the absence of tumors. We present this small series of patients who represent a diagnostic challenge.
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d
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Fig 1. Primary cutaneous diffuse large B-cell lymphoma, leg type. Patient 1. Annular lesion on the leg. A small scar represents the site from which the biopsy specimen was obtained.
Fig 2. Primary cutaneous diffuse large B-cell lymphoma, leg type. Patient 1. Histopathologic and phenotypical studies reveal (A) a moderately dense, perivascular infiltrate (B) characterized by small lymphocytes admixed with several large cells. The cells are positive for (C) CD20, (D) Bcl-2, and (E) MUM-1 and (F) show a high proliferation as detected by the antibody Ki-67.
lymphocytes admixed with large cells positive for CD20, Bcl-2, MUM-1, and focally for Bcl-6 and negative for CD3, CD4, CD56, CD30, and TdT. The proliferation rate detected with the Ki-67 antibody was [80%. In situ hybridization for EBER-1 was negative. A PCR study for Borrelia burgdorferi was negative. A diagnosis of cDLBCL-LT was made. Hemocrome and cytofluorometry of peripheral blood, CT scans of the thorax and abdomen, and bone marrow biopsy specimens were negative. The patient underwent local radiotherapy in June and July 2013 for a total dose of 46 Gy with complete remission. In April 2014, she presented with a 4-cm
erythematous, infiltrated plaque on her left thigh. The diagnosis of recurrent cDLBCL-LT was confirmed histopathologically and phenotypically. Staging investigations were again negative. Considering the age of the patient and the comorbidities, our tumor board decided to repeat radiotherapy, which was carried out and which achieved complete remission. At last follow-up in November 2014, she was free of disease.
DISCUSSION We described 3 patients with cDLBCL-LT characterized at onset by patches or thin plaques, some with annular morphology rather than thick plaques
4 Massone et al
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n 2015
Fig 3. Primary cutaneous diffuse large B-cell lymphoma, leg type. Patient 2. Annular erythematous patch on the ankle.
Fig 4. Primary cutaneous diffuse large B-cell lymphoma, leg type. Patient 2. The biopsy specimen reveals (A) a moderately dense perivascular and interstitial infiltrate (B) characterized by small lymphocytes admixed with several large cells. Note the high proliferation detected by the antibody Ki-67 (B, inset).
or tumors.1-3,7 To the best of our knowledge, this is the first report of this clinical presentation of cDLBCL-LT. Ekmekci et al6 described a 60-year-old man with cDLBCL-LT and a 6-month history of asymptomatic annular lesions on his right calf, but the lesions were nodules rather than the infiltrated patches seen in our patients. We have observed a similar patchy lesion in 1 patient with cDLBCL-LT who, 4 years after the first presentation with a tumor on the lower leg, experienced a recurrence on 1 arm characterized clinically by a slightly infiltrated erythematous patch and histopathologically by a moderately dense, specific infiltrate of the lymphoma (data not shown). A case reported clinically as ‘‘invisible’’ cDLBCL-LT was characterized by multiple, generalized subcutaneous tumors and B symptoms (ie, fever, night sweats, and weight loss),8 and probably did not represent a cDLBCL-LT but rather a diffuse large B-cell lymphoma. The clinical differential diagnosis in the cases that we reported includes several inflammatory
dermatoses that may have similar morphologic features, and particularly granuloma annulare, necrobiosis lipoidica, sarcoidosis, erythema annulare centrifugum, and erythema marginatum. In regions endemic for Borrelia infection, such as Austria, erythema chronicum migrans also represents an important differential diagnosis. In fact, patient 1 had been treated with antibiotics because of this presumptive diagnosis. Another interesting aspect is that all 3 patients reported long-standing lesions (present for 6, 9, and 18 months, respectively) that were stable or only slowly growing. In spite of the delay to obtain a biopsy specimen, all 3 cases were characterized histopathologically by only moderately dense infiltrates, consistent with the unremarkable clinical appearance of the lesions. Aside from the clinical challenge, this peculiar variant of cDLBCL-LT also represents a histopathologic pitfall. In fact, the typical diffuse, dense infiltrates involving the entire dermis and subcutis were lacking. In contrast, these cases presented
J AM ACAD DERMATOL
VOLUME jj, NUMBER j
Massone et al 5
In conclusion, we reported an unusual clinical presentation of cDLBCL-LT that deviates from the conventional one and that represents a formidable diagnostic challenge. Biopsy specimens of unusual patches, thin plaques, or annular lesions on the legs of adult patients should be obtained if the lesions do not respond to conventional treatment.
Fig 5. Primary cutaneous diffuse large B-cell lymphoma, leg type. Patient 3. Infiltrated erythematous patch on the leg.
with primarily perivascular, superficial, and deep lymphoid infiltrates composed of small reactive lymphocytes admixed with variable numbers of large lymphocytes with a B-cell phenotype and positivity for Bcl-2 and MUM-1. The histopathologic differential diagnosis includes primarily inflammatory dermatoses, such as acrodermatitis chronica atrophicans, morphea (inflammatory stage), lupus erythematosus, erythema gyratum, leprosy, and drug reaction. Complete phenotypic analyses are paramount in order to classify these cases properly. In this context, staining with Ki-67 is a good diagnostic tool because it shows the remarkably high proliferation rate of the infiltrate, which is inconsistent with inflammatory conditions. ‘‘Inflammatory dermatosiselike’’ infiltrates have also been described in early lesions of cutaneous follicle center lymphoma, diffuse type,9 and in specific skin manifestations of myelogenous leukemia,10 but clinical, pathologic, and phenotypical analyses allow clinicians to easily distinguish these malignant hematologic disorders.
REFERENCES 1. Willemze R, Swerdlow SH, Harris NL, Vergier B. Primary cutaneous follicle centre lymphoma. In: Swerdlow SH, Campo E, Harris NL, et al., eds. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon, France: IARC Press; 2008:227-228. 2. Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005;105:3768-3785. 3. Cerroni L. Cutaneous diffuse large B-cell lymphoma, leg-type. In: Cerroni L, ed. An illustrated guide to skin lymphoma. 4th ed. Oxford (UK): Blackwell Publishing; 2014:220-231. 4. Garbea A, Dippel E, Hildenbrand R, et al. Cutaneous large B-cell lymphoma of the leg masquerading as a chronic venous ulcer. Br J Dermatol. 2002;146:144-147. 5. S€ uss A, Simon JC, Sticherling M. Primary cutaneous diffuse large b-cell lymphoma, leg type, with the clinical picture of chronic venous ulceration. Acta Derm Venereol. 2007;87: 169-170. 6. Ekmekci TR, Koslu A, Sakiz D, Barutcuoglu B. Primary cutaneous large B-cell lymphoma, leg type, presenting with a migratory lesion. J Eur Acad Dermatol Venereol. 2007;21: 1000-1001. 7. Grange F, Beylot-Barry M, Courville P, et al. Primary cutaneous diffuse large b-cell lymphoma, leg type. Clinicopathologic features and prognostic analysis in 60 cases. Arch Dermatol. 2007;143:1144-1150. 8. Antic D, Petrovic N, Pelemis M, et al. ‘‘Invisible’’ primary cutaneous diffuse large B-cell lymphoma, leg type, as a cause of fever of unknown origin. J Clin Oncol. 2013;31: e276-e279. 9. Gulia A, Saggini A, Wiesner T, et al. Clinicopathologic features of early lesions of primary cutaneous follicle center lymphoma, diffuse type: implications for early diagnosis and treatment. J Am Acad Dermatol. 2011;65:991-1000. 10. Martınez-Escaname M, Zuriel D, Tee SI, et al. Cutaneous infiltrates of acute myelogenous leukemia simulating inflammatory dermatoses. Am J Dermatopathol. 2013;35:419-424.
ARTICLE
Atypical clinicopathologic presentation of primary cutaneous diffuse large B-cell lymphoma, leg type Cesare Massone, MD, Regina Fink-Puches, MD, Ingrid Wolf, MD, Iris Zalaudek, MD, and Lorenzo Cerroni, MD Graz, Austria Background: Primary cutaneous diffuse large B-cell lymphoma, leg type (cDLBCL-LT) is a well-defined entity of cutaneous B-cell lymphoma affecting predominantly elderly patients, mostly women. The typical clinical presentation is characterized by solitary or multiple, rapidly growing plaques or tumors on 1 leg (rarely both legs). Objective: We sought to describe a new clinical variant of cDLBCL-LT that deviates from the conventional one. Methods: Clinical, histopathologic, phenotypical, and molecular features of 3 cases of cDLBCL-LT presenting with patches or thin plaques were reviewed (all were women, aged 60, 62, and 87 years; lesions were located on the leg in all patients). Results: These patients presented with patches or thin plaques that represented the first manifestation of cDLBCL-LT. All 3 patients reported a history of long-standing lesions (present for 6, 9, and 18 months, respectively). Histology revealed moderately dense, perivascular infiltrates of small lymphocytes admixed with variable numbers of large cells that were CD201, Bcl-21, and MUM-11. Limitations: There were only a small number of cases. Conclusions: We reported an unusual clinical presentation of cDLBCL-LT that deviates from the conventional one and that represents a formidable diagnostic challenge. Biopsy specimens of unusual patches/thin plaques or annular lesions should be obtained from the legs of adult patients if the lesions do not respond to conventional treatment. ( J Am Acad Dermatol http://dx.doi.org/10.1016/j.jaad.2015.02.1134.) Key words: annular erythema; clinical presentation; cutaneous B-cell lymphoma; primary cutaneous diffuse large B-cell lymphoma; leg type.
P
rimary cutaneous diffuse large B-cell lymphoma, leg type (cDLBCL-LT) is a welldefined entity of cutaneous B-cell lymphoma (CBCL) affecting predominantly elderly patients, mostly women.1-3 In most cases, the clinical presentation is characterized by solitary or localized, sometimes ulcerated plaques or tumors located on 1 or both legs. In rare cases, large, ulcerated lesions may be clinically difficult to differentiate from venous leg ulcers.3-5 Another rare clinical presentation with a migratory lesion has been described in 1 patient.6 From the Dermatopathology Research Unit, Department of Dermatology, Medical University of Graz. Funding sources: None. Conflicts of interest: None declared. Accepted for publication February 24, 2015. Correspondence to: Lorenzo Cerroni, MD, Department of Dermatology, Medical University of Graz, Auenbruggerplatz 8, A-8036 Graz, Austria. E-mail: [email protected].
Abbreviations used: CBCL: cDLBCL-LT: PCR:
cutaneous B-cell lymphoma cutaneous diffuse large B-cell lymphoma, leg type polymerase chain reaction
We have recently observed 3 patients with cDLBCL-LT with an atypical presentation characterized by variably large erythematous, infiltrated Published online March 27, 2015. 0190-9622/$36.00 Ó 2015 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2015.02.1134
1
J AM ACAD DERMATOL
2 Massone et al
n 2015
radiotherapy, achieving complete remission. At last follow-up in December 2014, she was free of lesions. Patient 2. A 62-year-old woman presented to our department in June 2007 with a 9-month history of a slowly enlarging, asymptomatic erythematous lesion REPORT OF 3 CASES on her right ankle. The clinical examination revealed Patient 1. A 60-year-old woman presented a 10- 3 7-cm annular, slightly infiltrated erythemain January 2014 with an asymptomatic 10- 3 8-cm tous patch (Fig 3). Her medical annular patch with eryhistory was relevant only for thematous, well-defined CAPSULE SUMMARY hypothyroidism. She was borders and apparently taking levothyroxine, pentoxnormal skin in the center Primary cutaneous diffuse large B-cell ifylline, and acetylsalicylic (Fig 1). The lesion had lymphoma, leg type is characterized acid. A 4-mm biopsy specimen appeared 6 months earlier. clinically by solitary or localized, was obtained that revealed a The patient was living in sometimes ulcerated plaques or tumors moderately dense perivascua region endemic for located on 1 or both legs. lar and interstitial infiltrate in Borrelia, and in December We report 3 cases of cutaneous diffuse the papillary and reticular 2013 her general practilarge B-cell lymphoma, leg type with an dermis. The infiltrate was tioner treated her with atypical presentation characterized by composed by small lymphodoxycycline (200 mg/day) variably large erythematous, partly cytes admixed with large, for 3 weeks under a preannular patches or thin plaques in the atypical cell that were positive sumptive diagnosis of absence of tumors. for CD20, Bcl-2, Bcl-6 erythema chronicum mi(focally), and MUM-1 and grans, but without any Biopsy specimens of unusual patches/ negative for CD3, CD4, CD56, improvement. A clinical thin plaques or annular lesions on the CD30, and TdT (Fig 4). Small examination did not reveal legs of elderly patients should be reactive lymphocytes were any other lesion. Her obtained if the lesions do not respond to also present. In situ hybridizamedical history revealed conventional treatment. tion for EBER-1 was negative. Hashimoto thyroiditis with The proliferation rate detected hypothyroidism, osteopewith the Ki-67 antibody was [80%. PCR for Borrelia nia, arterial hypertension, and hypercholesterolemia burgdorferi was negative. A diagnosis of cDLBCL-LT treated with levothyroxine, cholecalciferol, was made. Hemocrome and cytofluorometry of bisoprolol, and simvastatin. Routine laboratory peripheral blood, CT scans of the thorax and investigations were within normal limits. A 4-mm abdomen, and bone marrow biopsy specimens did biopsy specimen was obtained that revealed a not reveal pathologic alterations. The patient was normal epidermis, dilated vessels in the dermis, treated with systemic chemotherapy (R-CHOP) and a perivascular infiltrate composed of large followed by autologous stem cell transplantation lymphocytes that were positive for CD20, PAX-5, with complete remission. In January 2009, she Bcl-2, MUM-1, and focally Bcl-6 and negative for developed a cutaneous relapse on her right leg CD3, CD4, CD56, CD30, and TdT (Fig 2). Small followed by rapid systemic dissemination. The reactive lymphocytes were also present. In situ patient died in February 2009. hybridization for EpsteineBarr virus (EBER-1) was Patient 3. An 87-year-old woman was referred to negative. The proliferation rate detected with the our department in April 2013 because of an Ki-67 antibody was [80%. A polymerase chain asymptomatic, erythematous thin plaque on her left reaction (PCR) analysis for Borrelia burgdorferi leg (Fig 5). The lesion appeared 18 months earlier, and was negative. A diagnosis of early stage cDLBCL-LT she reported slow enlargement of the lesion. was made. Complete staging investigations inclusive The clinical examination revealed an 8- 3 7.5-cm of hemocrome of peripheral blood, computed erythematous thin plaque on the left leg. She was tomography (CT) scans of the thorax and abdomen, taking bisoprolol and spironolactone for blood a bone marrow biopsy specimen, and cytofluoromhypertension, simvastatin for hypercholesteroetry of peripheral blood did not reveal lymphoma lemia, phenprocoumon for atrial fibrillation, and infiltration. Molecular analyses did not reveal a cholecalciferol for osteoporosis. Two 4-mm punch 14;18 translocation. In March 2014, the patient was biopsies were obtained, revealing similar features. treated with systemic chemotherapy (cyclophosphaHistology was characterized by a superficial and mide, hydroxydaunorubicin, vincristine, prednisodeep perivascular infiltrate composed of small lone, and rituximab [R-CHOP]) followed by local patches/thin plaques in the absence of tumors. We present this small series of patients who represent a diagnostic challenge.
d
d
d
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Massone et al 3
VOLUME jj, NUMBER j
Fig 1. Primary cutaneous diffuse large B-cell lymphoma, leg type. Patient 1. Annular lesion on the leg. A small scar represents the site from which the biopsy specimen was obtained.
Fig 2. Primary cutaneous diffuse large B-cell lymphoma, leg type. Patient 1. Histopathologic and phenotypical studies reveal (A) a moderately dense, perivascular infiltrate (B) characterized by small lymphocytes admixed with several large cells. The cells are positive for (C) CD20, (D) Bcl-2, and (E) MUM-1 and (F) show a high proliferation as detected by the antibody Ki-67.
lymphocytes admixed with large cells positive for CD20, Bcl-2, MUM-1, and focally for Bcl-6 and negative for CD3, CD4, CD56, CD30, and TdT. The proliferation rate detected with the Ki-67 antibody was [80%. In situ hybridization for EBER-1 was negative. A PCR study for Borrelia burgdorferi was negative. A diagnosis of cDLBCL-LT was made. Hemocrome and cytofluorometry of peripheral blood, CT scans of the thorax and abdomen, and bone marrow biopsy specimens were negative. The patient underwent local radiotherapy in June and July 2013 for a total dose of 46 Gy with complete remission. In April 2014, she presented with a 4-cm
erythematous, infiltrated plaque on her left thigh. The diagnosis of recurrent cDLBCL-LT was confirmed histopathologically and phenotypically. Staging investigations were again negative. Considering the age of the patient and the comorbidities, our tumor board decided to repeat radiotherapy, which was carried out and which achieved complete remission. At last follow-up in November 2014, she was free of disease.
DISCUSSION We described 3 patients with cDLBCL-LT characterized at onset by patches or thin plaques, some with annular morphology rather than thick plaques
4 Massone et al
J AM ACAD DERMATOL
n 2015
Fig 3. Primary cutaneous diffuse large B-cell lymphoma, leg type. Patient 2. Annular erythematous patch on the ankle.
Fig 4. Primary cutaneous diffuse large B-cell lymphoma, leg type. Patient 2. The biopsy specimen reveals (A) a moderately dense perivascular and interstitial infiltrate (B) characterized by small lymphocytes admixed with several large cells. Note the high proliferation detected by the antibody Ki-67 (B, inset).
or tumors.1-3,7 To the best of our knowledge, this is the first report of this clinical presentation of cDLBCL-LT. Ekmekci et al6 described a 60-year-old man with cDLBCL-LT and a 6-month history of asymptomatic annular lesions on his right calf, but the lesions were nodules rather than the infiltrated patches seen in our patients. We have observed a similar patchy lesion in 1 patient with cDLBCL-LT who, 4 years after the first presentation with a tumor on the lower leg, experienced a recurrence on 1 arm characterized clinically by a slightly infiltrated erythematous patch and histopathologically by a moderately dense, specific infiltrate of the lymphoma (data not shown). A case reported clinically as ‘‘invisible’’ cDLBCL-LT was characterized by multiple, generalized subcutaneous tumors and B symptoms (ie, fever, night sweats, and weight loss),8 and probably did not represent a cDLBCL-LT but rather a diffuse large B-cell lymphoma. The clinical differential diagnosis in the cases that we reported includes several inflammatory
dermatoses that may have similar morphologic features, and particularly granuloma annulare, necrobiosis lipoidica, sarcoidosis, erythema annulare centrifugum, and erythema marginatum. In regions endemic for Borrelia infection, such as Austria, erythema chronicum migrans also represents an important differential diagnosis. In fact, patient 1 had been treated with antibiotics because of this presumptive diagnosis. Another interesting aspect is that all 3 patients reported long-standing lesions (present for 6, 9, and 18 months, respectively) that were stable or only slowly growing. In spite of the delay to obtain a biopsy specimen, all 3 cases were characterized histopathologically by only moderately dense infiltrates, consistent with the unremarkable clinical appearance of the lesions. Aside from the clinical challenge, this peculiar variant of cDLBCL-LT also represents a histopathologic pitfall. In fact, the typical diffuse, dense infiltrates involving the entire dermis and subcutis were lacking. In contrast, these cases presented
J AM ACAD DERMATOL
VOLUME jj, NUMBER j
Massone et al 5
In conclusion, we reported an unusual clinical presentation of cDLBCL-LT that deviates from the conventional one and that represents a formidable diagnostic challenge. Biopsy specimens of unusual patches, thin plaques, or annular lesions on the legs of adult patients should be obtained if the lesions do not respond to conventional treatment.
Fig 5. Primary cutaneous diffuse large B-cell lymphoma, leg type. Patient 3. Infiltrated erythematous patch on the leg.
with primarily perivascular, superficial, and deep lymphoid infiltrates composed of small reactive lymphocytes admixed with variable numbers of large lymphocytes with a B-cell phenotype and positivity for Bcl-2 and MUM-1. The histopathologic differential diagnosis includes primarily inflammatory dermatoses, such as acrodermatitis chronica atrophicans, morphea (inflammatory stage), lupus erythematosus, erythema gyratum, leprosy, and drug reaction. Complete phenotypic analyses are paramount in order to classify these cases properly. In this context, staining with Ki-67 is a good diagnostic tool because it shows the remarkably high proliferation rate of the infiltrate, which is inconsistent with inflammatory conditions. ‘‘Inflammatory dermatosiselike’’ infiltrates have also been described in early lesions of cutaneous follicle center lymphoma, diffuse type,9 and in specific skin manifestations of myelogenous leukemia,10 but clinical, pathologic, and phenotypical analyses allow clinicians to easily distinguish these malignant hematologic disorders.
REFERENCES 1. Willemze R, Swerdlow SH, Harris NL, Vergier B. Primary cutaneous follicle centre lymphoma. In: Swerdlow SH, Campo E, Harris NL, et al., eds. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon, France: IARC Press; 2008:227-228. 2. Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005;105:3768-3785. 3. Cerroni L. Cutaneous diffuse large B-cell lymphoma, leg-type. In: Cerroni L, ed. An illustrated guide to skin lymphoma. 4th ed. Oxford (UK): Blackwell Publishing; 2014:220-231. 4. Garbea A, Dippel E, Hildenbrand R, et al. Cutaneous large B-cell lymphoma of the leg masquerading as a chronic venous ulcer. Br J Dermatol. 2002;146:144-147. 5. S€ uss A, Simon JC, Sticherling M. Primary cutaneous diffuse large b-cell lymphoma, leg type, with the clinical picture of chronic venous ulceration. Acta Derm Venereol. 2007;87: 169-170. 6. Ekmekci TR, Koslu A, Sakiz D, Barutcuoglu B. Primary cutaneous large B-cell lymphoma, leg type, presenting with a migratory lesion. J Eur Acad Dermatol Venereol. 2007;21: 1000-1001. 7. Grange F, Beylot-Barry M, Courville P, et al. Primary cutaneous diffuse large b-cell lymphoma, leg type. Clinicopathologic features and prognostic analysis in 60 cases. Arch Dermatol. 2007;143:1144-1150. 8. Antic D, Petrovic N, Pelemis M, et al. ‘‘Invisible’’ primary cutaneous diffuse large B-cell lymphoma, leg type, as a cause of fever of unknown origin. J Clin Oncol. 2013;31: e276-e279. 9. Gulia A, Saggini A, Wiesner T, et al. Clinicopathologic features of early lesions of primary cutaneous follicle center lymphoma, diffuse type: implications for early diagnosis and treatment. J Am Acad Dermatol. 2011;65:991-1000. 10. Martınez-Escaname M, Zuriel D, Tee SI, et al. Cutaneous infiltrates of acute myelogenous leukemia simulating inflammatory dermatoses. Am J Dermatopathol. 2013;35:419-424.
