Halo Nevi Are Not Trivial: About 2 Young Patients of Regressed Primary Melanoma That Simulates Halo Nevi.

BACKGROUND: Halo nevi are often considered benign, and the possibility of malignancy is not always clear to practitioners. We present two case reports suggesting that a halo nevus appearance can be seen in melanoma, even in young adults. A literature search for halo nevi revealing melanoma shows that this is a very rare condition. Case presentation. This report of two young patients indicates the importance of obtaining a detailed history to detect warning signs such as itching, pain, spontaneous bleeding, and previous alterations according to the patient, including a previously totally black colour in an already fully regressed melanoma. CONCLUSIONS: The risk of a halo nevus being malignant is higher if there is only one unique halo nevus and no personal or familial history of vitiligo. We postulate that a regressing atypical nevus or a regressing melanoma may be induced by an immunologic reaction as halo nevus type of clinical picture.

[Transitory apocrine hidrocystomatosis of the scrotum]. / Hidrocystomatose apocrine transitoire du scrotum.

BACKGROUND: Apocrine hidrocystomas are benign cystic tumors that develop from apocrine gland proliferation. In most cases, they are translucent solitary lesions of the face, generally found in the periorbital region, on the scalp or on the neck. More rarely, apocrine hidrocystomas may be multiple and appear on the ears, trunk, shoulders and genital area. They generally appear in adulthood, with only a few pediatric cases being reported, of which three in the genital area, with a solitary case of multiple hidrocystomas of the scrotum, although no cases of spontaneous involution of hidrocystomas have previously been reported. PATIENTS AND METHODS: Two boys aged 4 and 6 months were seen in consultation for small sub-millimeter size, subcutaneous, black lesions on the scrotum that appeared in the weeks following birth. Histological examination of these lesions resulted in a diagnosis of apocrine hidrocystoma. The children were seen again a few weeks later and the skin lesions had totally disappeared. We report two cases of multiple apocrine hidrocystomas on the scrotum with spontaneous involution diagnosed in a 4- and a 6-month-old boy. DISCUSSION: Apocrine hidrocystomas are rare benign adnexal tumors that develop from apocrine sweat glands. They are considered as cystic proliferations of the apocrine glands rather than simple retention cysts. The main differential diagnosis of the rare cases of multiple apocrine hidrocystomas are eccrine hidrocystomas. The treatment of such lesions is based on surgical excision if they are isolated, daily application of topical atropine 1%, or CO2 laser for multiple apocrine hidrocystomas.

A Rare Extraskeletal Osteosarcoma Appearing After 55 Years on a Large Stage 3 Burn Scar.

It is widely accepted that chronic burn wounds may lead to the development of various malignant skin tumors. Deep stage 3 burned areas may facilitate deeper carcinogenesis. Deep tissues are probably less subject to severe insult than is the epithelial layer during physical insult, suggesting that soft tissues transform to a lesser extent during the late stages of tumoral development as in an immunocompromised district with altered local immune defense with both cellular and humoral defense affected. Most authors claim that tumors are almost squamous cell carcinomas, although other types of malignancies such as basal cell carcinoma and, to a lesser extent, melanoma can also be seen. However, malignant transformation of cutaneous soft tissue in a burn insult area has rarely been described. Similarly, burn-induced tumors of histiocytic origin have been reported in few cases and osteosarcoma only in two case reports. Here, we report a patient case suffering from severe large stage 3 burn after-effects on the leg. Fifty-five years after the injury, this patient developed a large extraosseous osteosarcoma on the scar.

[Multiple cephalic deep granuloma annulare of children]. / Granulomes annulaires profonds multiples céphaliques de l'enfant.

BACKGROUND: Deep granuloma annulare is a fairly rare variety of granuloma annulare. It is seen predominantly in children and mainly affects the anterior aspect of the legs and the top of the feet; cephalic presentation is rare. Below, we report three cases of deep granuloma annulare in children presenting solely at the cephalic extremity. PATIENTS AND METHODS: Case 1: a six-year-old boy presented 7 cutaneous nodules measuring 1 to 2cm that were flesh-coloured, insensitive to palpation, of hard consistency and deeply attached. The lesions were grouped together on the anterior half of the left temporal fossa. While spontaneous regression of the three nodules was noted in the month following cutaneous biopsy, these nodules recurred a few months later. Case 2: a four-year-old girl with five deep cephalic nodules measuring around one centimetre and the colour of normal skin were seen on her right temporal fossa. The child was lost to follow-up after biopsy. Case 3: a four-month-old infant was presenting some 15 deep cutaneous nodules arranged in linear fashion on the forehead next to the left temporal fossa. These nodules regressed spontaneously one month after biopsy. In all three cases, histological examination confirmed the diagnosis of deep granuloma annulare. DISCUSSION: There have been few published cases of multiple, cephalic, deep granuloma annulare at a single site in children. The condition has an extensive differential diagnosis that includes malignant tumours; in addition, histological confirmation is normally essential. Treatment is not qualified and therapeutic extension with clinical monitoring alone may frequently be recommended.

Unusual Localisation for Onychomatricoma on the 5th Toenail: A Case Report and Review of the Literature.

Onychomatricoma is a rare and benign tumour of the nail matrix but originates rarely from the ventral portion of the proximal nail fold. This tumour is characterised by fingerlike projections that invade the nail plate. This lesion, of unknown aetiology, is typically asymptomatic with slow progression. Localisation on the finger is the most frequently described. We report the case of a 68-year-old woman who has an onychomatricoma in an unusual location, the fifth toe of the left foot. Due to its clinical appearance, the tumour can be confused with and treated as onychomycosis. However, if it is resistant to an oral antifungal well behaved treatment, one must consider onychomatricoma diagnosis.

Availability of digital dermoscopy in daily practice dramatically reduces the number of excised melanocytic lesions: results from an observational study.

BACKGROUND: Digital dermoscopy has been shown to permit an earlier detection of melanoma. However, few studies have investigated its added value in reducing unnecessary excisions in everyday clinical practice. OBJECTIVES: To compare, in daily practice, the efficiency of three dermoscopy methods: dermoscopy alone with little training, dermoscopy alone with adequate training and dermoscopy with adequate training and access to digital dermoscopy, and to confirm the safety of this latter approach. METHODS: Thirty-six dermatologists working without digital dermoscopy were divided into two groups according to their training in dermoscopy. The third group constituted of two dermatologists working in a pigmented lesion clinic with access to the digital dermoscopy technique and eight additional dermatologists working in the same dermatology department. These 46 dermatologists included all presumed melanocytic lesions excised over a period of 1 year. The primary endpoint was the melanoma/nonmelanoma ratio (M/NM-R); secondary endpoints were the ratio of 'problem' naevi to common naevi (PN/CN-R), specificity and sensitivity for the diagnosis of melanoma, in situ/invasive melanoma ratio, and the mean Breslow thickness. RESULTS: In total, 1865 excised lesions, including 231 melanomas, were included. In the digital dermoscopy availability group (DD-G) the M/NM-R was significantly better (1/2.43), as was the PN/CN-R (1/1.48) (P < 0.001 in both cases). The specificity was significantly higher in the DD-G and significantly higher for trained examiners as compared with examiners with little training. More that one-third of all melanomas discovered by digital dermoscopy were in situ, and the mean Breslow thickness was 0.32 mm for the invasive ones. CONCLUSIONS: The reduction of unnecessary excisions when using digital dermoscopy compared with dermoscopy alone in our study suggests that access to digital dermoscopy offers a better management of pigmented lesions in daily practice. The high number of early lesions diagnosed by this technique confirms that its use is safe.

HIV-associated multicentric Castleman disease: a report of 4 cases and review of the literature.

BACKGROUND: Multicentric Castleman's disease (MCD) is a rare, non-clonal lymphoproliferative disorder characterized by constitutional symptoms, anaemia and generalised lymphadenopathy. Its incidence among the HIV-positive population seems to have increased during the past decades. AIM: The present study intends to compare demographic features, clinical presentation, laboratory studies, imaging results as well as treatment regimens and outcome in our MCD patients to those of larger reported series. METHOD: We reviewed the files of 920 HIV-1-infected patients from our AIDS Reference Centre. Data was collected from the operating software for the patients' medical records of our institution (Medical Explorer v3r3, Cliniques St Luc, 2008). RESULTS: We report a series of four cases of MCD among our HIV/AIDS patients' cohort. Three were of African origin. They were diagnosed after 2003, after a mean duration of 54 months of HIV-seropositivity (ranging from 7 to 120 months) All presented with characteristic clinical features and laboratory findings, and were started on HAART a few months before or upon MCD diagnosis. Three patients were treated with chemotherapy (ABV), and one with HAART only. One patient who was given ABV is in continuous remission after 3 years of follow-up. The remaining three are alive, with good symptom control, regardless of the treatment they received. CONCLUSION: MCD is a rare, but rising issue among HIV-infected patients. The clinical and paraclinical features of our series of four patients are in keeping with those of larger reported series. Currently, treatment is mainly chemotherapy-based, but a wide variety of protocols have been used, mainly because of the lack of available evidence. New approaches such as anti-CD 20 antibodies seem highly effective, and the role of HHV-8 needs to be further investigated, as it might be an important target for future treatment. In light of this review, we are looking forward to offer these opportunities to our patients, despite unhelpful regulations.

Rituximab treatment induces the expression of genes involved in healing processes in the rheumatoid arthritis synovium.

OBJECTIVE: Rituximab displays therapeutic benefits in the treatment of patients with rheumatoid arthritis (RA) resistant to tumor necrosis factor (TNF) blockade. However, the precise role of B cells in the pathogenesis of RA is still unknown. We undertook this study to investigate the global molecular effects of rituximab in synovial biopsy samples obtained from anti-TNF-resistant RA patients before and after administration of the drug. METHODS: Paired synovial biopsy samples were obtained from the affected knee of anti-TNF-resistant RA patients before (time 0) and 12 weeks after (time 12) initiation of rituximab therapy. Total RNA was extracted, labeled according to standard Affymetrix procedures, and hybridized on GeneChip HGU133 Plus 2.0 slides. Immunohistochemistry and quantitative real-time reverse transcriptase-polymerase chain reaction experiments were performed to confirm the differential expression of selected transcripts. RESULTS: According to Student's paired t-tests, 549 of 54,675 investigated probe sets were differentially expressed between time 0 and time 12. Pathway analysis revealed that genes down-regulated between time 0 and time 12 were significantly enriched in immunoglobulin genes and genes involved in chemotaxis, leukocyte activation, and immune responses (Gene Ontology annotations). In contrast, genes up-regulated between time 0 and time 12 were significantly enriched in transcripts involved in cell development (Gene Ontology annotation) and wound healing (Gene Set Enrichment Analysis). At baseline, higher synovial expression of immunoglobulin genes was associated with response to therapy. CONCLUSION: Rituximab displays unique effects on global gene expression profiles in the synovial tissue of RA patients. These observations open new perspectives in the understanding of the biologic effects of the drug and in the selection of patients likely to benefit from this therapy.

Detection, identification and in vivo treatment responsiveness of bone morphogenetic protein (BMP)-activated cell populations in the synovium of patients with rheumatoid arthritis.

OBJECTIVE: To characterise the bone morphogenetic protein (BMP) target cells positive for phosphorylated (P)-SMAD1/5, in rheumatoid arthritis (RA) synovium. METHODS: Synovial biopsies were obtained by needle arthroscopy. Anti-P-SMAD1/5 antibodies were used for Western blot (WB) on protein extracts from RA and normal synovium and for immunostaining of synovial biopsy sections. Positive cells were further identified by double staining for CD3, CD20, CD68, CD138, CD90, alpha smooth muscle actin (SMA), endoglin (CD105) and von Willebrand factor (VWF). In sections from early patients with RA taken before and under antirheumatic treatment, the degree of inflammation and activation of the BMP pathway were quantified. RESULTS: P-SMAD1/5 protein was detected by WB in RA and to a lesser extent in normal synovium. Different P-SMAD1/5 positive cell populations were identified in RA synovium, mainly in perivascular and sublining cells. P-SMAD1/5 positive perivascular cells were alphaSMA positive and located around VWF positive endothelial cells. Some CD90 positive synovial fibroblasts were P-SMAD1/5 positive, as was part of the CD68 positive synovial cells but other cells of the haematopoietic lineage showed no SMAD1/5 phosphorylation. Treatment resulted in an absolute but not relative decrease in BMP activation in the synovium. CONCLUSION: BMP-activated cells belong to distinct stromal compartments in RA synovium and some of them express markers associated with the mesenchymal progenitor cell lineage. Antirheumatic treatment effectively downregulates synovial inflammation, but BMP activation in the synovium does persist albeit reduced.

Autologous stem-cell transplantation as consolidation therapy for diffuse large B-cell lymphoma patients with overexpression of bcl-2 protein. Results of the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trial LNH98-B2.

BACKGROUND: Overexpression of B-cell lymphoma 2 (bcl-2) protein is a simple biological adverse prognostic factor that could delimit the poor prognosis population candidate for improvement with high-dose therapy and autologous stem-cell transplantation (ASCT) in diffuse large B-cell lymphoma (DLBCL). Therefore, we conducted a risk-adapted phase II study with ASCT as consolidation therapy in low-intermediate risk (LIR) International Prognostic Index patients aged < or = 60 years with bcl-2 overexpression (bcl-2+). PATIENTS AND METHODS: Induction chemotherapy consisted of four courses of adriamycin, cyclophosphamide, vindesine, bleomycin, prednisone, once every 2 weeks. Responding bcl-2+ patients received ASCT as consolidation, and those without bcl-2 overexpression (bcl-2-) conventional chemotherapy. Three hundred and sixteen LIR patients with DLBCL, aged between 18 and 60 years, were included. Of these, 177 (56%) were bcl-2+ and 139 (44%) bcl-2-. RESULTS: Complete response rates after induction chemotherapy were similar in bcl-2+ and bcl-2- patients (74% versus 78%). Estimated 2-year event-free survival and disease-free survival for the bcl-2+ subgroup were 79% and 87%, for bcl-2- 84% and 92% and for the whole series 81% and 90%, respectively. CONCLUSIONS: These results demonstrate that taking into account biological characteristics in prospective multicenter trials allow successful adjustment of treatment and indicate that ASCT may counteract the adverse prognostic value of bcl-2 overexpression in responding LIR patients.

Identification of distinct gene expression profiles in the synovium of patients with systemic lupus erythematosus.

OBJECTIVE: Synovitis is a common feature of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), but the pattern of joint involvement differs in each disease. This study was undertaken to investigate the global gene expression profiles in synovial biopsy tissue from the swollen knees of untreated SLE patients (n = 6), RA patients (n = 7), and osteoarthritis (OA) patients (n = 6). METHODS: Synovial biopsy samples were obtained from the affected knees of patients in the 3 groups by needle arthroscopy. Half of the material was used for extraction of total RNA, amplification of complementary RNA, and high-density oligonucleotide spotted hybridization arrays. On the remaining tissue samples, real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical experiments were performed to confirm the microarray data. RESULTS: SLE synovial biopsy tissue displayed a significant down-regulation of genes involved in extracellular matrix (ECM) homeostasis and a significant up-regulation of interferon-inducible (IFI) genes. Real-time RT-PCR experiments confirmed the up-regulation of selected IFI genes (IFI27, IFI44, and IFI44L) in the SLE synovial tissue. Immunohistochemical analyses showed that 3 molecules involved in ECM regulation, chondroitin sulfate proteoglycan 2, latent transforming growth factor beta binding protein 2, and fibroblast activation protein alpha, were significantly down-regulated in SLE synovium. In contrast, immunostaining for IFI27, Toll-like receptor 4, and STAT-1 resulted in higher quantitative scores in SLE synovial tissue, which could be attributed to the fact that the RA samples had a large population of inflammatory cell infiltrates that were negative for these markers. CONCLUSION: Arthritis in SLE has a very distinct molecular signature as compared with that in OA and RA, characterized by up-regulation of IFI genes and down-regulation of genes involved in ECM homeostasis.

FOXP1, a gene highly expressed in a subset of diffuse large B-cell lymphoma, is recurrently targeted by genomic aberrations.

The transcription factor Forkhead box protein P1 (FOXP1) is highly expressed in a proportion of diffuse large B-cell lymphoma (DLBCL). In this report, we provide cytogenetic and fluorescence in situ hybridization (FISH) data showing that FOXP1 (3p13) is recurrently targeted by chromosome translocations. The genomic rearrangement of FOXP1 was identified by FISH in three cases with a t(3;14)(p13;q32) involving the immunoglobulin heavy chain (IGH) locus, and in one case with a variant t(2;3) affecting sequences at 2q36. These aberrations were associated with strong expression of FOXP1 protein in tumor cells, as demonstrated by immunohistochemistry (IHC). The cases with t(3p13) were diagnosed as DLBCL ( x 1), gastric MALT lymphoma ( x 1) and B-cell non-Hodgkin's lymphoma, not otherwise specified ( x 2). Further IHC and FISH studies performed on 98 cases of DLBCL and 93 cases of extranodal marginal zone lymphoma showed a high expression of FOXP1 in approximately 13 and 12% of cases, respectively. None of these cases showed, however, FOXP1 rearrangements by FISH. However, over-representation of the FOXP1 locus found in one additional case of DLBCL may represent another potential mechanism underlying an increased expression of this gene.

Tracking the follicular lymphoma cells in flow cytometry: characterisation of a new useful antibody combination.

OBJECTIVES: Follicular lymphoma (FL) is the most common adult non-Hodgkin's lymphoma. Diagnosis is based on morphology and can be confirmed by cytogenetic, flow cytometry (FCM) or molecular studies. Despite all these complementary approaches, diagnosis sometimes remains difficult. The purpose of the present work was to characterise the expression of new specific follicular cells markers which allows us to target specifically the abnormal FL cell population in FCM. METHODS: A total of 153 samples from healthy subjects and from patients with chronic B-cell lymphoproliferative disorders were analysed by FCM in the same conditions for purpose of comparison. RESULTS: We showed that CD44 is weakly expressed in FL cells compared with peripheral blood mononuclear cell from normal blood donors and others cells from B lymphoproliferative diseases. We nevertheless observed bone marrow samples where some immature B-cell population express CD44 with lower fluorescence intensity. Therefore, we developed a double antibody combination, using CD44 and CD38, which allowed us to separate the normal immature cells from the pathological population using FCM. CONCLUSION: This new phenotypic approach offers an accurate (sensitivity and specificity of 93% and 96%, respectively), fast and low sample consuming method for the diagnosis of FL.

Clinical and pathological features of 14 non-Hodgkin's lymphomas associated with coeliac disease.

BACKGROUND: It is well established that enteropathy associated T-cell lymphoma is associated with malabsorption which is due to gluten sensitivity (coeliac disease). Our study was performed to define the clinical features, histological subtypes, response to treatment, and outcome of the association of coeliac disease and T-cell lymphoma. PATIENTS AND METHODS: A retrospective study was performed in the UCL Group of Hematology to collect data on patients with a diagnosis of non-Hodgkin's lymphoma and coeliac disease. Fifteen cases were observed between 1985 and 1999. Case records for all but one patient were available and the pathological specimens of 14 patients were reviewed by two pathologists. RESULTS: Six previously diagnosed coeliac patients developed lymphoma; interval between coeliac symptoms and onset of the lymphoma ranged from 2 to 48 years (median 16 years). Five patients had coeliac disease and non-Hodgkin's lymphoma diagnosed concomitantly or less than 6 months before the symptoms leading to the diagnosis of lymphoma. Three patients had the diagnosis of coeliac disease after lymphoma diagnosis (1, 8 and 10 years later respectively). Ten non-Hodgkin's lymphomas were of T-cell origin and 4 were B-cell lymphomas. Eight out of 14 presented on a surgical emergency. Thirteen were treated using chemotherapy. The median survival from the diagnosis of enteropathy associated T-cell lymphoma was 12 months (range 1-126). CONCLUSIONS: Lymphomas associated with coeliac disease are heterogeneous and their diagnosis is difficult. The enteropathy-associated T-cell lymphoma is the most frequent, aggressive and fatal complication of coeliac disease but it is not rare to observe association with B-cell lymphoma. Chemotherapy is highly toxic in those patients. Despite a poor prognosis, long-term survival can be expected in a fraction of these patients.

Coexistence of BCL1/CCND1 and CMYC aberrations in blastoid mantle cell lymphoma: a rare finding associated with very poor outcome.

A patient with mantle cell lymphoma (MCL) of the pleomorphic blastoid subtype is reported. The disease was clinically aggressive and refractory to chemotherapy, and the patient survived only 2 months. Cytogenetically, a t(11;19;14)(q13;q13;q32) was found. Fluorescent in situ hybridization (FISH) and molecular analyses demonstrated involvement of the BCL1/CCND1 locus in a three-way translocation. In addition, subclonal abnormalities of the region 8q24 manifested either as a t(8;22)(q24;q11)/CMYC rearrangement or trisomy 8 were identified. The pathogenetic impact of this very uncommon association of BCL1/CCND1 and CMYC rearrangements in MCL is discussed and the literature is reviewed.

Epstein-Barr virus-associated lymphoproliferative disease occurring in a patient with sarcoidosis treated by methotrexate and methylprednisolone.

We describe the case of a 51-yr-old man with systemic sarcoidosis, complicated by the occurrence of a lymphoproliferative disease following a 36-month (duration) immunosuppressive treatment with methotrexate (MTX) and methylprednisolone. Four years after the onset of sarcoidosis, the patient presented a large necrotizing anal fistula. Pathological examination of this lesion showed a diffuse polymorphic infiltrate containing large Epstein-Barr virus (EBV)-positive lymphoid cells associated with areas of necrosis, all features similar to classical B-cell lymphoproliferative disorders occurring in immunosuppressed solid-organ recipients. MTX has been recently implicated in the development of lymphoproliferative disease in connective tissue diseases. This case supports the hypothesis that immunosuppression therapy may contribute to an increased risk for the development of EBV-associated lymphoproliferative disorders in patients suffering from sarcoidosis.

Angioimmunoblastic lymphadenopathy following ciprofloxacin administration.

Angioimmunoblastic lymphadenopathy (AILD) is a rare disorder characterised by generalised lymphadenopathy, fever, hepatosplenomegaly, immune hemolytic anemia and polyclonal hypergammaglobulinemia. We report the occurrence of histology-proven AILD in a patient who had received ciprofloxacin. We suggest that this drug may be added to the list of agents susceptible to elicit AILD.

Expression of gene MAGE-A4 in Reed-Sternberg cells.

Genes of the MAGE-A family are expressed in several types of solid tumors but are silent in normal tissues with the exception of male germline cells, which do not carry HLA molecules.Therefore, peptides encoded by MAGE-A genes are strictly tumor-specific antigens that can be recognized by CTL and constitute promising targets for immunotherapy. The expression of 6 genes of the MAGE-A family was tested with reverse transcriptase-polymerase chain reaction in lymphoma samples. Among 38 samples of non-Hodgkin lymphoma, 1 anaplastic large cell lymphoma expressed genes MAGE-A1, -A2, -A3, -A4, and -A12, and 1 lymphoepithelioid T-cell lymphoma expressed gene MAGE-A4. Five of 18 samples (28%) from patients with Hodgkin disease expressed gene MAGE-A4. In tissue sections, staining by a monoclonal antibody that recognizes the MAGE-A4 protein was observed in 11 of 53 samples (21%) from patients with Hodgkin disease. In the positive samples, the Reed-Sternberg cells were strongly stained whereas the surrounding cells were not. These results indicate that Hodgkin disease may be a target for specific immunotherapy involving MAGE-A4 antigens.