Abstract

INTRODUCTION

Primary cutaneous B-cell lymphomas (PCBCLs) are less frequent than cutaneous T-cell lymphomas, with incidence rates varying considerably between European (ranges from 20 to 25% of all PCBCL) and north American studies (ranges from 3.2 to 7.7%).[1] Nowadays the new World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification for cutaneous lymphomas identifies four main types of PCBCLs: 1) primary cutaneous marginal zone B-cell lymphoma; 2) primary cutaneous follicle center lymphoma; 3) primary cutaneous large B-cell lymphoma, leg type (PCLBCL-LT); 4) primary cutaneous large B-cell lymphoma, other.[2]

There are many unanswered questions concerning the homing of B-cells to the skin and their predilection to stay localized in the cutis. In the skin, there are no known equivalents to Peyer's patches of the intestinal tract or Waldeyer's ring of the pharynx. It has been postulated that skin and draining lymph nodes form an integrated system whereby a lympho-proliferative response to an antigenic stimuli may be elicited in the skin.[3] Therefore, primary cutaneous B-cell lymphoma (PCBCL) may be due to neoplastic amplification of this process and may be considered skin-associated lymphoid tissue-related B-cell lymphomas.[3]

CASE REPORTS

DISCUSSION

Approximately 27% of non-Hodgkin lymphomas occur in extranodal sites, and the skin is the second most common site of extranodal involvement after the gastrointestinal tract.[4] PCLBCL-LT is diagnosed by the presence of medium sized to large B lymphoid cells in diffuse sheets with round nuclei and conspicuous nucleoli that express BCl-2. In this update of the classification, the localization on the leg is incidental to the immunohistological aspects, which represent the diagnostic criteria, irrespective of the site of the onset. This explains the new term “leg type” instead of the previous “of the leg” in EORTIC, 1997 classification. In the WHO, 2001 classification this entry was known as diffuse large B-cell lymphoma (DLBCL), which later on grouped as PCLBCL-LT in the latest WHO, 2008 classification. Location other than legs have been reported to be sporadic even in the large series of patients, in particular trunk localization is found in 7.5-13.3% of all PCLBCL-LT.[5] Prognosis of PCLBCL-LT depends on pathologic features such as age of the patient, presence of multiple skin lesions (but not spread of single lesion) and disease duration.[5–7]

PCLBCL-LT usually affects the elderly patients with a female preponderance.[5,6] This subset comprise of approximately 1-3% of all cutaneous lymphomas and 5-105 of PCBCL.[8] It has intermediate clinical behavior and 5-year survival rate is 41%.[2] It presents as unique red or violaceous rapidly growing nodule or plaque, frequently ulcerated and located in the lower limb. Our cases are unusual for presentation in younger patients (age ranging between 26 and 38 years) compared to mean age of presentation (70 years) published in the literature.[2,5] Moreover, one of the two lesions was non ulcerated that is an uncommon finding in PCLBCL-LT.

The tumor cells of PCLBCL-LT express monotypic SIg and Cig, C19, C20, CD22, and CD79A. These lymphomas generally strongly express the BCL-2 protein, but are not associated with the interchromosomal t (14; 18) translocation. BCI-6 is expressed by most of the cases but CD10 is negative. In our cases, IHC analysis showed expression of CD20, CD19, MUM-1, Bcl-6 and BCl-2 by tumor cells whereas they were negative for CD10, CD30, EMA, CD5, and CD3. Both BCl-6 and BCl-2 expression were seen in our two cases. Later on one patient died with extracutaneous dissemination (brain involvement). The adverse prognostic impact of the BCl-2 expression has recently been substantiated by gene expression profiling studies showing high expression levels of apoptosis-including cytotoxic effector genes, which lead to constitutive inhibition of apoptotic pathways in the neoplastic cells.[9]

Radiotherapy is less effective in PCL BCL-LT and relapse rate was 58%. Extracutaneous progression was found in 30% of the cases.[10] Recent reviews suggest that PCL BCL-LT should be treated as systemic DLBCL with multiagent chemotherapy with or without rituximab.[2] Some suggest that these patients should be treated with various combinations of age-adapted, anthracycline containing chemotherapies and rituximab have a better outcome than patients receiving other treatments. Nowadays, R-CHOP with or without IFRT is considered as first line of treatment in PCL BCL-LT but the efficiency of this approach is still poorly documented.[10] Because follow up of the group treated with this protocol was insufficient (mean follow up period less than 2 years) to determine a statistically significant difference. In our case, both the patients received the R-CHOP+IFRT. During 1-year follow up period, one patient died with extracutaneous dissemination while the other patient is asymptomatic.

To conclude, PCL BCL-LT is a very rare type of cutaneous lymphoma and clinically it should be regarded as DLBCL. Though current recommendation to treat these cases is R-CHOP+IFRT, more controlled clinical trials are needed before coming to a conclusion.

Footnotes