R.M. Pujol

Primary cutaneous marginal zone B-cell lymphoma : a clinical, histopathological, immunophenotypic and molecular genetic study of 22 cases

Summary Background  Primary cutaneous marginal zone B‐cell lymphoma (MZCL) has recently been described. Differentiation from follicular centre cell lymphomas and lymphocytomas is often difficult due to insufficient experience and a lack of large series of patients.

Intralesional rituximab in the treatment of indolent primary cutaneous B-cell lymphomas: an epidemiological observational multicentre study. The Spanish Working Group on Cutaneous Lymphoma

Summary Background  Intravenous rituximab is a safe and effective option for the treatment of systemic non‐Hodgkin B‐cell lymphoma. The effectiveness of intralesional rituximab (ILR) in primary cutaneous B‐cell lymphomas (PCBL) has been described in a small number of patients.

Recurrent and self-healing cutaneous monoclonal plasmablastic infiltrates in a patient with AIDS and Kaposi sarcoma.

Infection with human immunodeficiency virus (HIV) increases the risk of developing non‐Hodgkin lymphoma. Plasmablastic lymphoma (PBL) is a rare variant of diffuse large cell lymphoma that often involves the oral cavity of HIV+ patients. It is characterized by immunoblastic morphology and plasma cell phenotype. Cutaneous involvement in PBL appears to be rare. We report a 44‐year‐old man with AIDS and Kaposi sarcoma (KS) previously treated with doxorubicin who, following treatment with highly active antiretroviral therapy, developed an erythematous infiltrated nodule on the right arm. Histology showed subcutaneous fat necrosis and clusters of atypical large plasma cells (plasmablastic cells). Immunohistochemistry revealed λ light chain restriction. Epstein–Barr virus (EBV) mRNA was detected by in situ hybridization within the plasmablastic cells. Polymerase chain reaction amplification with specific primers for human herpesvirus 8 (HHV‐8) performed on the skin biopsy specimen detected a specific band. A complete screening (bone marrow biopsy, computed tomographic scan, radiological survey) disclosed no abnormalities. The lesion resolved spontaneously after 3 months. Two years later an infiltrated plaque developed on the abdominal wall. The clinical and histopathological features of this new lesion were similar to those observed 2 years previously. No evidence of extracutaneous involvement was detected. The lesion again resolved spontaneously after 25 days. PBL may be seen in patients with transplants or receiving chemotherapy, but is usually observed in patients with advanced AIDS. The observation of recurrent self‐healing EBV‐ and HHV‐8‐associated cutaneous monoclonal plasmablastic infiltrates, in a patient with AIDS and KS, expands the clinical spectrum of AIDS‐associated plasmablastic lymphoproliferative disorders.

Sézary Syndrome and Related Variants of Classic Cutaneous T-cell Lymphoma. A Descriptive and Prognostic Clinicopathologic Study of 29 Cases*

Large series of patients with Sézary syndrome (SS), the leukemic variant of cutaneous T-cell lymphoma (CTCL), have been reported infrequently because of its low incidence. Here we recorded several clinical, histopathological and immunophenotypical features of 29 cases of leukemic CTCL patients from four Dermatology Departments of Catalonia, Spain, and analyzed their prognostic value. Clinical data included sex, age, delay of SS diagnosis, previous diagnosis of lymphoma, B-symptoms, type of skin lesions, peripheral adenopathy, histologic evaluation of lymph node biopsy, visceral involvement, percentage of circulating Sézary cells, serum LDH and beta-2-microglobulin levels, first treatment and response, disease-free interval, further therapies and survival. Histopathological data examined were epidermotropism, depth and thickness of the infiltrate, cell size, adnexal involvement, presence of granuloma, eosinophils and plasma cells, mitotic rate. The percentage of CD45Ro, CD43, CD20, CD30 and CD8 positive dermal cells were also recorded. Survival showed a mean actuarial risk of 57% at 3 years and 38% at 5 years, with a median survival of 48 months. Analysis of actuarial survival demonstrated as following as features linked with a bad prognosis: fast evolution of the disease (from symptoms onset up to diagnosis) (p =0.0274) raised levels of serum lactate dehydrogenase (p =0.0379) and beta-2-microglobulin (p =0.0151), the latter being the most important prognostic factor. In conclusion although SS had been traditionally considered as a low-grade lymphoma, the present study agrees with the recent classification rating SS as an aggressive type of CTCL with a poor prognosis. Our results show that some simple clinical and blood test data can be useful as prognostic indicators in this disease.

MYC gene numerical aberrations in actinic keratosis and cutaneous squamous cell carcinoma

Background  The genetic alterations that drive the transition from actinic keratoses (AKs) to cutaneous squamous cell carcinomas (SCCs) have not been defined precisely. Amplification and/or overexpression of the MYC proto‐oncogene have been demonstrated in several human, malignant tumours including head and neck SCCs.

Primary cutaneous B-cell lymphoma (marginal zone) with prominent T-cell component and aberrant dual (T and B) genotype; diagnostic usefulness of laser-capture microdissection

The presence of a dominant B‐ or T‐cell clone is an important diagnostic criterion for distinguishing cutaneous lymphomas from lymphoid reactive infiltrates. Rarely, a combined B‐ and T‐cell rearrangement can be detected from a single sample. In such instances, genotypic analysis does not permit differentiation of the coexistence of a T‐ and B‐cell lymphoma from a single clone harbouring a monoclonal rearrangement for both immunoglobulin heavy chain and T‐cell receptor genes. We herein report a case of a skin tumour consistent with a dense cutaneous lymphoid infiltrate showing a double prominent B‐ and T‐cell component. A dual B‐ and T‐cell clonality was detected by polymerase chain reaction from whole‐tissue DNA sample. Genotypic analysis with DNA, obtained after laser‐assisted microdissection from the B‐cell population, again showed both T‐ and B‐cell monoclonal rearrangements. Conversely, the microdissected T‐cell population did not reveal a clonal pattern. The diagnosis of cutaneous B‐cell lymphoma with a dual B‐ and T‐cell genotype was established. This description illustrates the diagnostic usefulness of laser‐capture microdissection in cutaneous lymphomas presenting dual genotype.

Kikuchi's disease (necrotizing lymphadenitis) with cutaneous involvement associated with subacute cutaneous lupus erythematosus

Necrotizing histiocytic lymphadenopathy (Kikuchis disease) is a rarely observed clinical entity characterized by fever, and solitary or multiple lymphadenopathy predominantly in the posterior cervical region. Kikuchis disease has been reported to precede, coexist with or follow the diagnosis of systemic lupus erythematosus. In only rare instances has its association with cutaneous lupus erythematosus without systemic involvement been reported. We report a 45‐year‐old woman who presented characteristic systemic and cutaneous manifestations of Kikuchis disease. Several months later, after sun exposure, she developed lesions of subacute cutaneous lupus erythematosus. The American Rheumatism Association criteria for systemic lupus erythematosus were not fulfilled. The possible pathogenic relationships between the two processes are discussed.

Primary Cutaneous CD30+ Anaplastic Large-Cell Lymphomas Show a Heterogeneous Genomic Profile: An Oligonucleotide ArrayCGH Approach

TO THE EDITOR Primary cutaneous CD30-positive lymphoproliferative disorders are the second most common group of primary cutaneous T-cell lymphomas (Willemze et al., 2005), after the mycosis fungoides/Sézary syndrome group. The clinical and histological features of primary cutaneous anaplastic large-cell lymphoma (C-ALCL) have been well characterized, but little is known about its underlying pathogenetic and genetic alterations. Previous comparative genomic hybridization (CGH) studies focusing on C-ALCL that included a limited number of samples yielded nonhomogeneous results (Böni et al., 2000; Mao et al., 2003; Prochazkova et al., 2003; Fischer et al., 2004; Zettl et al., 2004). Recently, three studies that were based on array CGH (aCGH) and included a small number of C-ALCL patients were published (Mao et al., 2003; Laharanne et al., 2010; van Kester et al., 2010). We have investigated the genomic profile of 19 C-ALCL patients using a 60-mer 44K oligonucleotide-arrayCGH platform and compared our results with those of previous aCGH studies. C-ALCL patients were selected according to the World Health Organization–European Organization for Research and Treatment for Cancer (EORTC) classification for cutaneous lymphomas (Willemze et al., 2005). This EORTC multicenter study was conducted in the departments of pathology and dermatology of six European centers in Spain and Switzerland. The local ethics committees approved the study, and written informed consent was obtained from all patients, in accordance the Declaration of Helsinki Principles. Clinical characteristics are detailed in Supplementary Table S1 online. The study was performed with 20 10 mm snap-frozen C-ALCL samples to ensure the high quality of the DNA. Hematoxylin–eosin staining of a frozen section of each sample was performed tumor cell infiltration of at least 70%. DNA was isolated using a commercial kit as described in manufacturer’s instructions (Dneasy Blood and Tissue Kit; Qiagen, Hilden, Germany). Genomewide analysis of patient samples was conducted using the Human Genome CGH 44K microarrays (G4410B and G4426B; Agilent Technologies, Palo Alto, CA), a whole-genome platform containing 44,000 probes along the entire human genome with a mean resolution of ±75 kb. Hybridization was performed according to the manufacturer’s protocols. Data analysis was conducted as previously described (Salgado et al., 2010). Fluorescence in situ hybridization with noncommercial probes of bacterial artificial chromosome DNA clones from the CHORI bacterial artificial chromosome/PAC resource (http://bacpac. chori.org) was performed to confirm chromosomal abnormalities previously detected by aCGH in cases for which a paraffin-embedded tissue biopsy was available. Chromosomal abnormalities were detected in 17 of 19 analyzed C-ALCL samples (89.5%). Losses were more frequently detected than gains (78.9 vs. 68.4%). Mao et al. (2003) and van Kester et al. (2010) found gains more frequently than losses, whereas Laharanne et al. (2010) detected losses more frequently. The highest frequencies of chromosomal aberrations were 60% (Mao et al., 2003) and 45% (Laharanne et al., 2010; van Kester et al., 2010), in contrast to 36.8% in our present study. Regarding the smallest overlapping regions of imbalance, 15 corresponded to losses and 9 to gains. The results are summarized in Figure 1 and detailed in Supplementary Table S2 online. The specific chromosomal regions and candidate genes mapped in these regions are detailed in Table 1. The most frequent abnormalities observed were deletions located on 16q, 13q, 17p13, and 20q13. Genomic losses of 13q34 (ING1) and 16q22.11 (CTCF) detected by aCGH were confirmed by fluorescence in situ hybridization in three patients. No significant correlation between the observed clinical features and the presence of chromosomal aberrations could be demonstrated. Furthermore, no data regarding the prognostic significance of the observed genetic results were obtained. In agreement with studies by van Kester et al. (2010) and Laharanne et al. (2010), two regions were lost in our study, at 13q33.3 and 16p11.2. These regions were not detected in the first aCGH study (Mao et al., 2003), probably because they may not have been among the 57 oncogenic regions of the AmpliOnc platform. Similar to the findings of van Kester et al. (2010), we observed losses at 3p26.3, 6q21, 8p22, 13q12.11, 13q13.1, 16p11.2-16q11.2, 17p13.1, and 17p13.3 (Supplementary Table S3 online). The main concordance between our results and those of van Kester et al. (2010) was a deletion at 16q11.2. However, differences were observed for a higher frequency of 16q losses in our series, including seven genomic regions located between 16q11.2 and 16q24.3. The most Abbreviations: aCGH, array comparative genomic hybridization; C-ALCL, primary cutaneous anaplastic large-cell lymphoma; CGH, comparative genomic hybridization

Acute myeloid dendritic cell leukaemia with specific cutaneous involvement: a diagnostic challenge.

Myeloid or type 1 dendritic cell leukaemia is an exceedingly rare haematopoietic neoplasm characterized by a specific immunophenotypic profile close to plasmacytoid dendritic cell and acute myelogenous leukaemia. A 77‐year‐old man presenting specific cutaneous infiltration by myeloid dendritic cell leukaemia is reported. The clinical features as well as the cutaneous histopathological and immunohistochemical features led to the initial diagnosis of CD4+/CD56+ haematodermic neoplasm. However, extensive immunophenotypic studies performed from peripheral blood blasts disclosed that leukaemic cells expressed myeloid dendritic cell markers, confirming the diagnosis. The diagnostic difficulties of specific cutaneous involvement by myeloid dendritic cell leukaemia on the basis of routine histopathological and immunohistochemical features are highlighted.

Solitary oral ulceration as the first appearance of lymphomatoid papulosis: a diagnostic challenge

Lymphomatoid papulosis (LyP) may involve any cutaneous site but the oral areas seems to be an unusual location. We report a 72‐year‐old patient who presented with a 1‐week history of a solitary oral ulcer on the lateral tongue, which had raised and indurated borders. Although squamous cell carcinoma was initially diagnosed, the morphological, phenotypical and genotypical studies confirmed diagnosis of LyP. We are not aware of previous reports of definite LyP presenting as oral lesions, which may pose a diagnostic challenge. The differential diagnosis includes several neoplastic, reactive and infectious disorders. LyP should be considered in patients showing solitary, rapidly developing ulcers with raised, indurated borders in the oral cavity.