Extracavitary primary effusion lymphoma presenting as a cutaneous tumor: a case report and literature review
Accepted Article
U. Pielasinski, MD1 C. Santonja, MD2 S.M. Rodríguez-Pinilla, MD2 L. Requena, MD1 Departments of Dermatology1 Pathology2 and Hematology,3 Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain. Correspondence: Luis Requena, MD, Department of Dermatology, Fundación Jiménez Díaz, Avda. Reyes Católicos 2, 28040-MAdrid, Spain. Phone: +34-91-5447039, Fax: +34-91-5442636, E-mail: [email protected]. Funding sources: None to declare Conflict of interest disclosures: None to declare ABSRACT primary effusion lymphoma is an unusual form of aggressive B-cell lymphoma universally associated with human herpesvirus 8 (HHV8) that involves mostly human immunodeficiency virus (HIV)-infected patients. Characteristically, it presents as a malignant serous effusion involving body cavities, but without associated tumor mass. Exceptionally, HHV8-positive lymphomas with features identical to primary effusion lymphoma may present as mass lesions in the absence of cavity effusions along the course of the disease, and are regarded as extracavitary or solid variants of the disorder. These rare forms are extremely rare in the skin.
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/cup.12368
This article is protected by copyright. All rights reserved.
We report a case of extracavitary primary effusion lymphoma arising in a HIV-infected male, who presented with two subcutaneous masses involving the skin of the abdominal
Accepted Article
and inguinal regions as the first manifestation of the process. Kaposi sarcoma was not present in the skin surface or mucous membranes. Extensive studies failed to demonstrate involvement of other organs and the case was considered as an example of extracavitary primary effusion lymphoma originating primarily in the skin.
Herein, we review the few reported cases of solid primary effusion lymphoma involving the skin in order to delineate the clinicopathologic, immunohistochemical, and molecular characteristics of this rare lymphoma in the skin.
INTRODUCTION Primary effusion lymphoma is an unusual form of non-Hodgkin lymphoma etiologically related to human herpesvirus 8 (HHV8) that usually presents as a lymphomatous effusion in the body cavities but without associated tumor masses (classic primary effusion lymphoma).1 Rare HHV8 positive lymphomas occurring as solid masses have been described and have been designated the extracavitary or solid variant of primary effusion lymphoma.2 This unique subtype presents similar histopathologic, immunohistochemical and genotypic characteristics to classic primary effusion lymphoma and it is also etiologically related with HHV8. We report a case of solid primary effusion lymphoma in a human immunodeficiency virus (HIV) infected young male who presented with abdominal and inguinal subcutaneous masses and a constitutional syndrome.
This article is protected by copyright. All rights reserved.
REPORT OF A PATIENT A 33-year-old Brazilian homosexual male had a previous history of HIV infection since
Accepted Article
2008. He started highly active antiretroviral therapy (HAART) in March 2012 due to increased viral load (1,078,920 copies/ml) (6.0 log) and decreased CD4+ T cells (288 cells/⎧L) in peripheral blood. He was referred to our Department of Dermatology in March of 2012 because of a periumbilical subcutaneous mass, which had been steadily enlarging for approximately 6 weeks. In addition, the patient reported asthenia, malaise and fever. Physical examination demonstrated a large erythematous indurate plaque measuring 10 x 15 cm involving the hypogastric area (Fig. 1A). No lesions clinically suggestive of Kaposi sarcoma were found in the skin surface or in mucous membranes. Utilizing a clinical diagnosis of panniculitis versus cutaneous lymphoma, an incisional biopsy was performed. Histopathologic examination revealed a lymphoproliferative process mainly located in subcutaneous tissue and extending to the lower part of the dermis. Neoplastic cells were large, with a plasmablastic appearance, and were characterized by pleomorphic and eccentric nuclei with prominent nucleoli and abundant eosinophilic cytoplasm. Mitotic figures were numerous (Fig. 2). Immunohistochemical studies demonstrated strong expression of the neoplastic cells for CD45/LCA, MUM1, BLIMP1 and CD138. CD30 immunoreactivity was also found in some aggregates of neoplastic cells. Kappa light chain mRNA was detected in the neoplastic cells by chromogenic in situ hybridization, whereas Lambda light chain was negative. The nuclei of the neoplastic cells also co-expressed immunoreactivity for the HHV8-latent associated latent protein (LAN), with a characteristic multiple dot-like staining pattern in all neoplastic cells, as well as EBER expression by in situ hybridization3 (Fig. 3). However, neoplastic cells resulted negative for CD20, CD79a, PAX5, CD3, CD2, CD4, CD8, CD7, CD5, CD56, bcl2, bcl6, and ALK. The proliferation index as determined by Ki-67
This article is protected by copyright. All rights reserved.
immunostaining was approximately 90%. PCR studies (Biomed primers)4,5 showed a clonal IgH peak while the rearrangements for TCR gene were polyclonal. FISH study
Accepted Article
for IgH/CMYC translocation6 was negative. A diagnosis of solid primary effusion lymphoma was established. Cutaneous masses disappeared spontaneously after two months with highly active antiretroviral therapy (HAART). Physical examination, peripheral blood, bone marrow biopsy and total body PET-TC studies failed to demonstrate internal involvement by the lymphoproliferative process.
In June 2012 the patient was referred again to our Department for a new lesion on his right inguinal region, which had increased rapidly in size, with associated constitutional syndrome. Physical examination demonstrated a firm, 10-cm in greatest dimension subcutaneous mass on the right inguinal fold (Fig. 1B), without involvement of the testicle. A new incisional biopsy was performed. Histopathologic and immunohistochemical findings were identical to those of the previous biopsy, showing a plasmablastic proliferation involving mainly the deep dermis and subcutis.
Laboratories studies demonstrated the following abnormalities: increased beta-2 microglobulin 3.47mg/L (normal range 0.9 – 2.0 mg/L) and elevated erythrocyte sedimentation rate (ESR) 45 mm/h (normal range
Accepted Article
U. Pielasinski, MD1 C. Santonja, MD2 S.M. Rodríguez-Pinilla, MD2 L. Requena, MD1 Departments of Dermatology1 Pathology2 and Hematology,3 Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain. Correspondence: Luis Requena, MD, Department of Dermatology, Fundación Jiménez Díaz, Avda. Reyes Católicos 2, 28040-MAdrid, Spain. Phone: +34-91-5447039, Fax: +34-91-5442636, E-mail: [email protected]. Funding sources: None to declare Conflict of interest disclosures: None to declare ABSRACT primary effusion lymphoma is an unusual form of aggressive B-cell lymphoma universally associated with human herpesvirus 8 (HHV8) that involves mostly human immunodeficiency virus (HIV)-infected patients. Characteristically, it presents as a malignant serous effusion involving body cavities, but without associated tumor mass. Exceptionally, HHV8-positive lymphomas with features identical to primary effusion lymphoma may present as mass lesions in the absence of cavity effusions along the course of the disease, and are regarded as extracavitary or solid variants of the disorder. These rare forms are extremely rare in the skin.
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/cup.12368
This article is protected by copyright. All rights reserved.
We report a case of extracavitary primary effusion lymphoma arising in a HIV-infected male, who presented with two subcutaneous masses involving the skin of the abdominal
Accepted Article
and inguinal regions as the first manifestation of the process. Kaposi sarcoma was not present in the skin surface or mucous membranes. Extensive studies failed to demonstrate involvement of other organs and the case was considered as an example of extracavitary primary effusion lymphoma originating primarily in the skin.
Herein, we review the few reported cases of solid primary effusion lymphoma involving the skin in order to delineate the clinicopathologic, immunohistochemical, and molecular characteristics of this rare lymphoma in the skin.
INTRODUCTION Primary effusion lymphoma is an unusual form of non-Hodgkin lymphoma etiologically related to human herpesvirus 8 (HHV8) that usually presents as a lymphomatous effusion in the body cavities but without associated tumor masses (classic primary effusion lymphoma).1 Rare HHV8 positive lymphomas occurring as solid masses have been described and have been designated the extracavitary or solid variant of primary effusion lymphoma.2 This unique subtype presents similar histopathologic, immunohistochemical and genotypic characteristics to classic primary effusion lymphoma and it is also etiologically related with HHV8. We report a case of solid primary effusion lymphoma in a human immunodeficiency virus (HIV) infected young male who presented with abdominal and inguinal subcutaneous masses and a constitutional syndrome.
This article is protected by copyright. All rights reserved.
REPORT OF A PATIENT A 33-year-old Brazilian homosexual male had a previous history of HIV infection since
Accepted Article
2008. He started highly active antiretroviral therapy (HAART) in March 2012 due to increased viral load (1,078,920 copies/ml) (6.0 log) and decreased CD4+ T cells (288 cells/⎧L) in peripheral blood. He was referred to our Department of Dermatology in March of 2012 because of a periumbilical subcutaneous mass, which had been steadily enlarging for approximately 6 weeks. In addition, the patient reported asthenia, malaise and fever. Physical examination demonstrated a large erythematous indurate plaque measuring 10 x 15 cm involving the hypogastric area (Fig. 1A). No lesions clinically suggestive of Kaposi sarcoma were found in the skin surface or in mucous membranes. Utilizing a clinical diagnosis of panniculitis versus cutaneous lymphoma, an incisional biopsy was performed. Histopathologic examination revealed a lymphoproliferative process mainly located in subcutaneous tissue and extending to the lower part of the dermis. Neoplastic cells were large, with a plasmablastic appearance, and were characterized by pleomorphic and eccentric nuclei with prominent nucleoli and abundant eosinophilic cytoplasm. Mitotic figures were numerous (Fig. 2). Immunohistochemical studies demonstrated strong expression of the neoplastic cells for CD45/LCA, MUM1, BLIMP1 and CD138. CD30 immunoreactivity was also found in some aggregates of neoplastic cells. Kappa light chain mRNA was detected in the neoplastic cells by chromogenic in situ hybridization, whereas Lambda light chain was negative. The nuclei of the neoplastic cells also co-expressed immunoreactivity for the HHV8-latent associated latent protein (LAN), with a characteristic multiple dot-like staining pattern in all neoplastic cells, as well as EBER expression by in situ hybridization3 (Fig. 3). However, neoplastic cells resulted negative for CD20, CD79a, PAX5, CD3, CD2, CD4, CD8, CD7, CD5, CD56, bcl2, bcl6, and ALK. The proliferation index as determined by Ki-67
This article is protected by copyright. All rights reserved.
immunostaining was approximately 90%. PCR studies (Biomed primers)4,5 showed a clonal IgH peak while the rearrangements for TCR gene were polyclonal. FISH study
Accepted Article
for IgH/CMYC translocation6 was negative. A diagnosis of solid primary effusion lymphoma was established. Cutaneous masses disappeared spontaneously after two months with highly active antiretroviral therapy (HAART). Physical examination, peripheral blood, bone marrow biopsy and total body PET-TC studies failed to demonstrate internal involvement by the lymphoproliferative process.
In June 2012 the patient was referred again to our Department for a new lesion on his right inguinal region, which had increased rapidly in size, with associated constitutional syndrome. Physical examination demonstrated a firm, 10-cm in greatest dimension subcutaneous mass on the right inguinal fold (Fig. 1B), without involvement of the testicle. A new incisional biopsy was performed. Histopathologic and immunohistochemical findings were identical to those of the previous biopsy, showing a plasmablastic proliferation involving mainly the deep dermis and subcutis.
Laboratories studies demonstrated the following abnormalities: increased beta-2 microglobulin 3.47mg/L (normal range 0.9 – 2.0 mg/L) and elevated erythrocyte sedimentation rate (ESR) 45 mm/h (normal range
