Treatment of multifocal primary cutaneous B-cell lymphoma: a clinical follow-up study of 29 patients.

PURPOSE: Although patients with primary cutaneous B-cell lymphoma (CBCL) and localized skin lesions are generally treated with radiotherapy and have an excellent prognosis, the clinical behavior and optimal treatment of CBCL presenting with multifocal skin lesions are less well defined. In this study, we evaluated the clinical behavior of and results of treatment for multifocal CBCL in 29 patients, and we formulated therapeutic guidelines. PATIENTS AND METHODS: The study group included 16 patients with primary cutaneous follicular center-cell lymphoma (PCFCCL), eight with primary cutaneous immunocytoma (PCI), and five with primary cutaneous large B-cell lymphoma presenting on the legs (PCLBCL of the leg). RESULTS: Only one of the 24 patients with multifocal PCFCCL or PCI developed extracutaneous disease, and no patient died from lymphoma (median follow-up, 54 months). In patients with PCFCCL, treatment with either multiagent chemotherapy (nine patients) or radiotherapy directed toward all skin lesions (five patients) proved equally effective in terms of complete remission, relapse, and survival. In contrast, all five patients with PCLBCL of the leg developed extracutaneous disease, and four of the five died from systemic lymphoma, 8 to 36 months (median, 21 months) after diagnosis. CONCLUSION: The results of these preliminary studies suggest that patients with PCFCCL or PCI presenting with multifocal skin lesions have the same excellent prognosis that patients with localized PCFCCL or PCI have and that radiotherapy directed toward all skin lesions is as effective as multiagent chemotherapy. Patients with PCLBCL of the leg have a more unfavorable prognosis, particularly patients presenting with multifocal skin lesions. This last group should always be treated with multiagent chemotherapy.

Primary cutaneous marginal zone B-cell lymphoma: clinical and therapeutic features in 50 cases.

BACKGROUND: Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is a low-grade B-cell lymphoma that originates in the skin, with no evidence of extracutaneous disease. Studies focusing on the optimal treatment of PCMZL have not been published thus far. We describe 50 patients with PCMZL to further characterize clinical characteristics and outcome and, in particular, to evaluate our current therapeutic approach. OBSERVATIONS: The majority of the patients (36/50 [72%]) presented with multifocal skin lesions, and 14 patients (28%) presented with solitary or localized lesions. The initial treatment of patients with solitary lesions consisted of radiotherapy or excision, whereas patients with multifocal lesions received a variety of initial treatments, most commonly radiotherapy and chlorambucil therapy. Cutaneous relapses developed in 19 (48%) of 40 patients who had complete remission and were more common in patients with multifocal disease. After a median period of follow-up of 36 months, 2 patients developed extracutaneous disease, but none of the patients died of lymphoma. CONCLUSIONS: Patients with PCMZL who have solitary lesions can be treated effectively with radiotherapy or excision. For patients with PCMZL who have multifocal lesions, chlorambucil therapy and radiotherapy are suitable therapeutic options. In case of cutaneous relapses, the beneficial effects of treatment should carefully be weighed against the potential adverse effects.

Demonstration of clonal immunoglobulin gene rearrangements in cutaneous B-cell lymphomas and pseudo-B-cell lymphomas: differential diagnostic and pathogenetic aspects.

Twenty-five patients with a benign or malignant cutaneous B-cell lymphoproliferative disease, including seven cutaneous pseudo-B-cell lymphomas, eight primary cutaneous B-cell lymphomas (CBCL), and 10 secondary cutaneous B-cell lymphomas, were investigated for the presence of clonal immunoglobulin (Ig) gene rearrangements using Southern blot hybridization analysis. The selection of pseudo-B-cell lymphomas was based on the presence of polyclonal light-chain expression with immunohistochemical analysis. All cases of CBCL demonstrated monotypic light-chain expression or absence of detectable Ig on CD20+ B cells. Clonal rearrangements of one or more Ig genes were demonstrated in four of seven cases of cutaneous pseudo-B-cell lymphomas, six of eight cases of primary CBCL, and in all cases of secondary CBCL. The observation that cutaneous pseudo-B-cell lymphomas as defined by immunohistochemical criteria often contain occult monoclonal B-cell populations implies that differentiating between pseudo-B-cell lymphomas and CBCL is not always possible by means of gene-rearrangement analysis. These findings may support the concept that cutaneous pseudo-B-cell lymphomas and primary CBCL are part of a continuous and progressive spectrum of B-cell lymphoproliferative skin disorders.

A translocation (8;14) in a cutaneous large B-cell lymphoma.

A 62-year-old man with a cutaneous large-cell (cleaved, noncleaved) lymphoma had multiple facial lesions and two enlarged cervical lymph nodes. Cytogenetic analysis performed on the involved skin and lymph node revealed the following karyotype: 47,XY,inv dup(1)(q11-->q32),+3,t(8;14)(q24;q32). A t(8;14)(q24;q32) translocation is the chromosome anomaly in 75% of Burkitt's lymphomas. Other types of non-Hodgkin's lymphomas, however, may show the same translocation, especially large-cell lymphomas. Duplication of material belonging to the long arm of chromosome 1 is the most frequent additional aberration to Burkitt's translocations in Burkitt's lymphoma/leukemia. Trisomy 3 may be seen in both B- and T-cell malignancies, as well as in angioimmunoblastic lymphadenopathy. Immunogenotyping of malignant cells from a lymph node showed rearrangement of the immunoglobulin heavy and lambda light chain genes. Epstein-Barr virus (EBV) serology was positive for EBV nuclear antigen and EBV capsular antigen. No integration of EBV DNA in tumor tissue, however, could be detected by polymerase chain reaction. These results may be useful in defining the biologic characteristics of cutaneous B-cell non-Hodgkin's lymphomas.

Use of monoclonal antibody KP1 for identifying normal and neoplastic human mast cells.

The monoclonal antibody KP1 (CD68) was used to stain normal and neoplastic monocytes and macrophages in routinely processed, paraffin wax embedded tissue: mast cells also exhibited strong, consistent cytoplasmic immunoreactivity. Light microscopic findings were corroborated by electron microscopical and immunocytochemical findings. The predominant sites of immunoreactivity were the specific intracytoplasmic granules of the mast cells. All mast cell subtypes--that is, normal and reactive mast cells, such as those in lymph nodes exhibiting chronic non-specific lymphadenitis, and malignant or neoplastic mast cells in various types of mastocytosis--reacted with this antibody. This finding is of diagnostic importance, because mast cell proliferation could be mistaken for histiocyte proliferation. It also supports the hypothesis that mast cells derive from the bone marrow.

Multiple clear cell acanthomas. A clinical, histological, and ultrastructural report.

A case of multiple clear cell acanthomas in a 64-year-old woman is reported. The clinical and histological findings of this rare entity are consistent with the hypothesis that clear cell acanthomas are benign epidermal tumors. An ultrastructural study was performed with special emphasis on the melanocytic-keratinocytic interaction.

The Bazex-Dupré-Christol syndrome.

BACKGROUND: The Bazex-Dupré-Christol syndrome is characterized by follicular atrophoderma, congenital hypotrichosis, and basal cell neoformations that include basal cell carcinomas and basal cell nevi. OBSERVATIONS: We describe a large family in which 20 persons across four generations present with typical features of the Bazex-Dupré-Christol syndrome. However, the clinical picture in this family differs with regard to gender and age. Male subjects have a uniformly severe disease, whereas female subjects exhibit a range of severity of the syndrome. The most striking difference between male and female subjects is provided by hypotrichosis. In male subjects, hypotrichosis is diffuse and affects all scalp hairs. On the other hand, female subjects do not have hypotrichosis, but normal hairs are intermingled with abnormal hairs. In infancy and childhood, multiple milia are present, whereas in adults only a few milia are observed. CONCLUSIONS: The family pedigree seems to be consistent with an X-linked inheritance, since male-to-male transmission does not occur. Moreover, further evidence of an X-linked dominant mode of inheritance could be derived from the observation of gender differences that can be attributed to the lyonization phenomenon in female subjects. From a clinical and morphologic point of view, the Bazex-Dupré-Christol syndrome seems to be a disorder of the hair follicle.

Primary cutaneous large B-cell lymphomas of the legs. A distinct type of cutaneous B-cell lymphoma with an intermediate prognosis. Dutch Cutaneous Lymphoma Working Group.

BACKGROUND AND DESIGN: Primary cutaneous follicular center cell lymphomas represent a distinct type of cutaneous B-cell lymphoma, clinically characterized by localized skin lesions on the head or trunk and an excellent prognosis. Histologically similar lymphomas may occur on the legs. The clinical behavior of this group is still undefined, and controversy exists whether these lymphomas should be classified as follicular center cell lymphoma or B-immunoblastic lymphoma. We reviewed the clinical, histologic, and follow-up data of 18 patients with primary cutaneous large B-cell lymphoma of the legs. RESULTS: Primary cutaneous large B-cell lymphoma of the legs generally occurred in elderly patients (median age at diagnosis, 76 years), in particular women (male-female ratio, 7:2), and preferentially affected the lower legs (14 of 18 patients). Radiotherapy and/or systemic polychemotherapy resulted in complete remissions in 16 of 17 patients. Follow-up data demonstrated estimated 2- and 5-year survival rates of 77% and 58%, respectively. Histologic evaluation showed diffuse dermal infiltrates with variable proportions of centroblasts (large noncleaved cells), large centrocytes (large cleaved cells), and B immunoblasts. Seventeen of 18 patients were diagnosed as having primary cutaneous follicular center cell lymphoma; only 1 patient, whose histologic examination showed more than 30% immunoblasts, was diagnosed as having B-immunoblastic lymphoma. CONCLUSIONS: Primary cutaneous large B-cell lymphoma of the legs is a distinct clinicopathologic entity that mainly affects elderly patients and has an intermediate prognosis. Although most cases have a follicular center cell origin, primary cutaneous large B-cell lymphoma is proposed as the most appropriate term for this type of cutaneous lymphoma.

Mycosis fungoides: disease evolution and prognosis of 309 Dutch patients.

OBJECTIVES: To determine the disease course of Dutch patients with mycosis fungoides and to define factors related to disease progression and survival. DESIGN: A multicenter, 13-year, retrospective cohort analysis. SETTING: Eight dermatology departments collaborating in the Dutch Cutaneous Lymphoma Group. PATIENTS: Three hundred nine patients with mycosis fungoides registered between October 1985 and May 1997, including 89 patients with limited patches or plaques (stage Ia), 135 with generalized patches or plaques (stage Ib), 46 with skin tumors (stage Ic), 18 with enlarged but uninvolved lymph nodes (stage II), 18 with lymph node involvement (stage III), and 3 with visceral involvement (stage IV). MAIN OUTCOME MEASURES: Response to initial treatment, sustained complete remission, actuarial disease progression, and overall and disease-specific survival per clinical stage. RESULTS: The median follow-up was 62 months (range, 1-113 months). For the entire group, the actuarial overall and disease-specific survival was 80% and 89% at 5 years, and 57% and 75% at 10 years, respectively. The actuarial 5-year disease-specific survival of patients with stage Ia, Ib, and Ic disease was 100%, 96%, and 80%, respectively, and only 40% for patients with stage III disease. Using multivariate analysis, the presence of extracutaneous disease, the type and extent of skin involvement, the response to initial treatment, and the presence of follicular mucinosis were independently associated with higher disease progression and mortality rates. The calculated risks of disease progression at 5 and 10 years gradually increased from 4% to 10% for those with stage Ia disease, from 21% to 39% for those with stage Ib disease, and from 32% to 60% for those with stage Ic disease; for those with stage III disease, the risk remained at 70% at 5 and 10 years. The overall risk of disease progression at 5 and 10 years was 24% and 38%, respectively, for the total study group. CONCLUSION: At least within the first 10 years after diagnosis, disease progression and mycosis fungoides-related mortality occur in only a subset of patients generally presenting with advanced disease.

Morphological changes in the proximal area of the rat's hair follicle during early catagen. An electron-microscopic study.

This electron-microscopic study of the catagen phase shows that the first alteration of regression of the follicle is localized in the papilla, where the cells withdraw their offshoots and break the contact with the basal lamina. Both at the level of the papilla and of the bulb structures appear that increase the cell cohesion. Under the influence of the outer root sheath an upward migration occurs. This is followed by plication and thickening of the basal lamina. The alterations in the connective tissue sheath occur in a further stage. The first signs of autolysis occur in the center of the epithelial column. At the end of the catagen stage macrophages take care of the clearing-up.

Mantle-cell lymphomas of the skin.

The skin lesions of two elderly women lead us to the diagnosis of small cleaved lymphocytic B-cell non-Hodgkin's lymphoma, TNM stage IVb after clinical staging examinations. Relapses occurred within less than 1 year. Morphology, enzymhistochemistry (alkaline phosphatase in the first case), and immunohistochemistry (CD 5 positivity in the second case) in the skin biopsies supported the diagnosis of mantle-cell lymphoma. The histogenesis of the mantle-cell lymphoma is reviewed.

Sucrose laurate gels as a percutaneous delivery system for oestradiol in rabbits.

In this study sucrose laurate was formulated in hydrogels and investigated as a suitable transdermal penetration enhancer for oestradiol. Using rabbits as an animal model, the absolute bioavailability and the skin irritation were evaluated after single and multiple application. Three hydrogels containing 60 mg% oestradiol were evaluated: Oestrogel, and two hypromellose gels containing 5 and 15% sucrose laurate (w/w), respectively. No stability problem of the sucrose laurate was detected during a storage period of four months at 7 +/- 2 degrees C. After single application no significant difference (P < 0.05) was observed between the bioavailability parameters of Oestrogel and the 5% sucrose laurate gel. The values obtained for the 15% sucrose laurate gel were significantly higher than for the other gels. When applied on day 7 after a 6-day treatment, twice daily with the respective placebo gel, no significant difference was seen amongst the three formulations for any of the parameters evaluated. When the results after multiple application were compared with those after single application, a significant increase in oestradiol bioavailability was seen for the gel containing 30% ethanol and a significant decrease in oestradiol bioavailability was seen for the 5 and 15% sucrose laurate gels. Histological evaluation of the untreated and treated skin biopsies, showed a significantly higher incidence of infiltrate for all treated skin biopsies in comparison with the untreated ones. A significant increase in skinfold thickness was seen for the skin biopsies treated with gel containing 15% sucrose laurate. It can be concluded that sucrose laurate shows a potential as an absorption enhancer for percutaneous drug delivery.

Lectin binding patterns of human tissue mast cells indicate marked phenotypical diversity.

Glycoconjugate expression by human tissue mast cells (MCs) from various sources (including lymph nodes with signs of chronic non-specific lymphadenitis, skin lesions of urticaria pigmentosa, and bone marrow infiltrates associated with systemic mastocytosis) was studied histochemically with a broad panel of fluorescein-labelled lectins. Of the 19 lectins applied, 11 (sugar specificities: fucose, N-acetylgalactosamine and neuraminic acid) did not stain any MCs, while 8 (sugar specificities: mannose, N-acetylglucosamine, and galactose) were found to bind to MCs. These lectins exhibited different binding patterns in various disease entities. Only a few of these 8 lectins (in particular, phythaemagglutinin-L) produced strong staining of the MCs in most or all of the cases. Some (e. g. phythemagglutinin-E) produced only weak staining, and this in only a few cases. The lectins used, however, did not distinguish between reactive and tumorous MCs. Although lectins are therefore unlikely to be of use in resolving problems of differential diagnosis concerning proliferation of MCs, our investigation has shown that tissue MCs exhibit marked phenotypical diversity with regard to their lectin-binding properties.

Cutaneous periarteritis nodosa. A case report.

We studied a patient with severe ulcerations on the lower limbs due to cutaneous periarteritis nodosa. Chronic relapsing course during more than 12 years with no systemic involvement was documented.

[Congenital diffuse melanosis]. / Mélanose diffuse congénitale.

Two cases of diffuse congenital melanosis are presented. The hyperpigmentation appeared shortly after birth and invades progressively the trunk and the limbs. It is diffuse and most intensive on the abdomen and the back, and reticulated on the neck, the genitals and in the groins. The nails are thin and their surface is slightly irregular. Histologic examination reveals the presence of melanin in the deep and superficial layers of the epidermis. On electron microscopy the melanosomes are not grouped within the keratinocytes, but are dispersed throughout the cytoplasm of the epidermal cells. The disease can be considered as an autonomous entity. The mechanism of the hyperpigmentation is not known.

[Herpes gestationis. A histological and electron microscopic study (author's transl)]. / Herpes gestationis. Etude histologique et ultrastructurale.

The histology and electron microscopy of two cases of herpes gestationis is described (HG). It appears that at the histological as well as at the ultrastructural level, the blister of HG results from degenerative changes in the basal cells and is initially located in the epidermis. It is associated with spongiosis. As a consequence of the disappearance of the basal cell layer, the blister is secondarily found between the malpighian layer and the subepidermal basement membrane. Immunologically, C3 could be found at that dermo-epidermal junction. Although the immunological findings can be similar to those of BP, it is believed that HG and BP must be considered as different entities, because of the very particular clinical features of HG and because the blister formation is different in both diseases.

[Cutaneous burns caused by Yperite. Apropos of 2 new cases]. / Brûlures cutanées à l'Ypérite. A propos de deux nouveaux cas.

Based on two of their own cases, the authors review the lesions produced by Yperite. This chemical agent produces cutaneous burns which are quite characteristic; histological study of biopsies carried out on cutaneous lesions was used to define the effects on the epidermis and dermis. The treatment of patients, with this rare condition, remains symptomatic.