Primary cutaneous marginal zone lymphoma

Primary cutaneous marginal zone lymphoma

Crit Rev Oncol Hematol. 2009 Oct 9

Dalle S, Thomas L, Balme B, Dumontet C, Thieblemont C.

Service de dermatologie, Université Claude Bernard Lyon I, Hospices Civils de Lyon, Lyon, France.

Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is included in the group of extranodal marginal zone B-cell lymphoma involving mucosal sites. Many evidences suggest that chronic antigen stimulation is a key-player in its pathogenesis. While Helicobacter pylori seems not to be implicated in PCMZL, Borrelia Burgdorferi's role is still matter of debate since the results are discordant between European and North American/Asian countries. However Borrelia subspecies are different between the studied areas and this difference could be a confounding factor. Then ubiquitous candidate antigen is still missing. Beyond these discrepancies the treatment of diffuse PCMZL has been recently improved. If local therapies (surgery, radiation) are the gold standard for localized disease, rituximab can also be considered as an alternative for disseminated or plurifocal PCMZL.

Elsevier

Primary cutaneous marginal zone B-cell lymphoma: clinical and histological aspects

Pathologica. 2009 Feb

Khaled A, Sassi S, Fazaa B, Ben Hassouna J, Ben Romdhane K, Kamoun MR.

Department of Dermatology, Charles Nicolle Hospital, Tunis, Tunisia. aida.khaled@rns.tn

According to the WHO-EORTC classification of cutaneous lymphomas, primary cutaneous marginal zone B-cell lymphoma are now well characterized. We report here a case of primary cutaneous marginal zone B-cell lymphoma in a 51 year-old man in which the diagnosis was made using both histology and immunopathology. The patient had no remarkable medical history, no history of either acute inflammation or insect bite, and presented with a 5 cm solitary asymptomatic erythematous firm, multinodular and infiltrated plaque on the back for 12 months. Histological examination and immunohistochemical study of a cutaneous biopsy provided a differential diagnosis between B cell lymphoma and lymphocytoma cutis. Full body work up revealed no signs of extracutaneous dissemination. The patient underwent surgical excision of the nodule. Histological examination showed a histological and immunophenotyping profile typical of primary cutaneous marginal zone B-cell lymphoma. The lesion was completely excised with clear margins and no recurrence occurred after a 12 month-follow-up period. Primary cutaneous marginal zone B-cell lymphoma are low-grade lymphomas that have an indolent course and a high tendency to recur. They should be differentiated from lymphocytoma cutis and from the other types of cutaneous B cell lymphomas that have a different course and prognosis.

PMID: 19771768 [PubMed - in process]

Vitreous metastases of primary cutaneous B-cell lymphoma.

Vitreous metastases of primary cutaneous B-cell lymphoma.

Ocul Immunol Inflamm. 2009 Sep-Oct

Chong DY, Johnson MW, Shen D, Chan CC, Callanan DG.

Texas Retina Associates, Arlington, TX, USA.

Purpose: To describe two cases of vitreous metastases of primary cutaneous B-cell lymphoma (PCBCL). Methods: Observational case series. Results: A 73-year-old man and an 81-year-old woman, both with a history of PCBCL, diffuse large cell type, presented with decreased visual acuity due to vitritis. Both patients underwent vitreous biopsy that demonstrated B-cell lymphoma, large cell type, and confirmed metastases of cutaneous B-cell lymphoma to the vitreous. Conclusion: PCBCL, diffuse large cell type, is a rare form of non-Hodgkin lymphoma that can metastasize to the vitreous without visible chorioretinal involvement.

PMID: 19831568 [PubMed - in process]

IRF4 Gene Rearrangements Define a Subgroup of CD30-Positive Cutaneous T-Cell Lymphoma

IRF4 Gene Rearrangements Define a Subgroup of CD30-Positive Cutaneous T-Cell Lymphoma:

A Study of 54 Cases

J Invest Dermatol. 2009 Oct

Pham-Ledard A, Prochazkova-Carlotti M, Laharanne E, Vergier B, Jouary T, Beylot-Barry M, Merlio JP.

Department of Histology and Molecular Pathology of Tumors, University Bordeaux 2, Bordeaux, France.

Correspondence: Professor Jean-Philippe Merlio, Department of Histology and Molecular Pathology, University Bordeaux 2, 146 rue Leo Saignat, Bordeaux 33076, France. E-mail:jp.merlio@u-bordeaux2.fr

The identification of IFN regulatory factor 4 gene (IRF4) translocation in 8 out of 14 cases of cutaneous anaplastic large cell lymphomas (C-ALCLs) (Leukemia, 2009; 23(3):574-80) prompted us to study IRF4 locus status in different cutaneous T-cell lymphoma (CTCL) subtypes. Fluorescence in situ hybridization (FISH) was used with break-apart dual-color probes. Sixty samples from 54 patients were analyzed with 23 C-ALCL, 11 transformed mycosis fungoides (T-MF), 7 lymphomatoid papulosis (LyP), and 13 Sézary syndrome (SS) cases. IRF4 immunostaining was performed in 32 cases. We observed a split FISH signal pattern indicating a translocation at the IRF4 locus in 6 out of 23 C-ALCL (26%) and 2 out of 11 T-MF (18.2%) cases. Extra copies of the IRF4 locus were found in 4 out of 13 SS, 1 out of 11 T-MF, and 1 out of 23 C-ALCL cases, corresponding to either aneuploidy, chromosome 6 trisomy, or 6p partial gain. The IRF4 expression was not correlated with the presence of IRF4 alteration in C-ALCL or T-MF. Interestingly, IRF4 rearrangements define a subgroup of CD30-positive C-ALCL and T-MF cases. Conversely, T-MF cases with IRF4 rearrangements may correspond to the development of C-ALCL in MF patients and not to large cell transformation. Investigation of the biological pathways triggered by IRF4 rearrangements and/or expression in CTCL will provide a biological basis for IRF4-directed therapy.Journal of Investigative Dermatology advance online publication, 8 October 2009; doi:10.1038/jid.2009.314.

Nature

Abbreviations:

ALCL, anaplastic large cell lymphoma; ALK, anaplastic lymphoma kinase; C-ALCL, cutaneous anaplastic large cell lymphoma; CTCL, cutaneous T-cell lymphoma; FISH, fluorescencein situ hybridization; IRF4, IFN regulatory factor 4; LyP, lymphomatoid papulosis; MF, mycosis fungoides; MM, multiple myeloma; MUM1, multiple myeloma antigen 1; PTCL, peripheral T-cell lymphoma; T-MF, transformed mycosis fungoides

Primary cutaneous marginal zone B-cell lymphoma: clinical and histological aspects.

Primary cutaneous marginal zone B-cell lymphoma: clinical and histological aspects.

Pathologica. 2009 Feb

Khaled A, Sassi S, Fazaa B, Ben Hassouna J, Ben Romdhane K, Kamoun MR.

Department of Dermatology, Charles Nicolle Hospital, Tunis, Tunisia. aida.khaled@rns.tn

According to the WHO-EORTC classification of cutaneous lymphomas, primary cutaneous marginal zone B-cell lymphoma are now well characterized. We report here a case of primary cutaneous marginal zone B-cell lymphoma in a 51 year-old man in which the diagnosis was made using both histology and immunopathology. The patient had no remarkable medical history, no history of either acute inflammation or insect bite, and presented with a 5 cm solitary asymptomatic erythematous firm, multinodular and infiltrated plaque on the back for 12 months. Histological examination and immunohistochemical study of a cutaneous biopsy provided a differential diagnosis between B cell lymphoma and lymphocytoma cutis. Full body work up revealed no signs of extracutaneous dissemination. The patient underwent surgical excision of the nodule. Histological examination showed a histological and immunophenotyping profile typical of primary cutaneous marginal zone B-cell lymphoma. The lesion was completely excised with clear margins and no recurrence occurred after a 12 month-follow-up period. Primary cutaneous marginal zone B-cell lymphoma are low-grade lymphomas that have an indolent course and a high tendency to recur. They should be differentiated from lymphocytoma cutis and from the other types of cutaneous B cell lymphomas that have a different course and prognosis.

PubMed

Anetoderma in cutaneous marginal-zone B-cell lymphoma.

Anetoderma in cutaneous marginal-zone B-cell lymphoma.

Clin Exp Dermatol. 2009 Sep

Zattra E, Pigozzi B, Bordignon M, Marino F, Chiarion-Sileni V, Alaibac M.

Department of Dermatology, University of Padua, Padua, Italy.

Correspondence to Dr Mauro Alaibac, Dermatology Unit, University of Padua, Via C. Battisti 206, 35128, Padova, Italy
E-mail: mauro.alaibac@unipd.it

Summary: Anetoderma is a rare condition, consisting of well-circumscribed areas of slack skin, in which dermal elastic fibres are destroyed or deficient. We present the case of a 45-year-old man with a 25-year history of deep nodules and plaques gradually progressing to areas of anetoderma. Histological examination found an infiltrate composed of neoplastic cells with lymphoplasmocytoid morphology. The cells were positive for CD20, CD38 and CD138, and there was a monoclonal kappa light chain gene rearrangement of plasma cells. A diagnosis of cutaneous marginal-zone B-cell lymphoma was made. The pathogenesis of anetoderma remains unknown, but it is possible that cytokines or other soluble factors produced by the infiltrating lymphocytes have a role in this process.

Wiley InterScience

Hodgkin lymphoma with cutaneous involvement

Hodgkin lymphoma with cutaneous involvement
May 2009

Hodgkin lymphoma with cutaneous involvement Cyrus C Hsia MD FRCPC1, Kang Howson-Jan MD FRCPC1, Kamilia S Rizkalla MD FRCPC2Dermatology Online Journal 15 (5): 5 1. Department of Medicine, Division of Hematology2. Department of PathologyLondon Health Sciences Centre, London, Ontario, Canada. chsia@uwo.ca

Abstract
We report a case of a 54-year-old previously healthy man with Hodgkin lymphoma who presented initially with a solitary cutaneous ulcer. Unlike non-Hodgkin lymphoma subtypes, skin involvement of Hodgkin lymphoma is extremely rare. Furthermore, the prognosis of Hodgkin lymphoma with skin infiltration is felt to be extremely poor. Contrary to other reports, this case demonstrates that a good response with standard therapy is possible.

Introduction
In contrast to non-Hodgkin lymphoma subtypes, skin involvement of Hodgkin lymphoma (HL) is extremely rare [1, 2]. Furthermore, the prognosis when cutaneous involvement is present is felt to be extremely poor in HL [2]. We report a case of a patient with HL who presented with a solitary cutaneous ulcer. Although his diagnosis was delayed, he obtained a good response with adequate standard therapy.

Case
A 54-year-old previously healthy man noticed an ulceration in his left gluteal area. Initially, the ulcer was the size of a quarter, but subsequently enlarged to 10 cm over the course of several months. The lesion had areas of necrotic and loose granulation tissue. Marked left inguinal lymphadenopathy with associated scrotal, penile, and left leg edema developed. These were also associated with mild intermittent fevers and significant weight loss.

Two separate biopsies of the ulceration were performed and both were reported as non-specific dermatitis. However, upon review by a hematopathologist (KSR, one of the authors) the diagnosis of classical Hodgkin lymphoma, nodular sclerosis subtype, was made. The biopsies revealed multinucleated giant cells with large nuclei and several nucleoli, the characteristics of Reed-Sternberg cells, underneath a large area of ulceration and necrosis. These cells were present in the typical background of small mature lymphocytes, eosinophils, and plasma cells.

A biopsy of a left inguinal lymph node confirmed the diagnosis of nodular sclerosis HL. Similar to the skin lesion, Reed-Sternberg cells were again present and stained positively for both CD15 and CD30. The lymph node had a typical nodular pattern surrounded by broad collagen bands. Staging CT scan of the abdomen showed massive conglomerated retroperitoneal lymphadenopathy. Bone marrow was otherwise unremarkable. He was diagnosed with stage 3B disease and was started on chemotherapy with ABVD (Adriamycin, Bleomycin, Vinblastine, and Dacarbazine) with an overall good response. After six weeks of treatment his ulcer had completely healed and his disease was deemed to be in complete remission after six cycles of therapy.

Discussion
Since the first description by Sir Thomas Hodgkin in 1832, the diagnosis, classification, and management of HL have evolved dramatically [3]. Hodgkin lymphoma represents a small but significant proportion of malignancies worldwide and has a bimodal age distribution [1, 3]. The etiology and pathogenesis of this disease remains unknown [1, 3]. A few risk factors such as familial predisposition, infections with Epstein-Barr virus or human immunodeficiency virus, and immune suppression have been implicated [1, 2, 3]. This disease has been divided into two major groups according to the World Health Organization: the rare nodular lymphocyte-predominant and classical Hodgkin lymphoma [1]. Classical HL contains four subtypes: nodular sclerosis, mixed cellularity, lymphocyte rich, and lymphocyte depleted [1]. Each subtype has its own clinical features, pathological characteristics and prognosis [1, 3].

The most common clinical manifestation of classical HL is painless lymphadenopathy; over 80 percent of involved lymph nodes are found above the diaphragm [1, 2]. Patients may also describe painful lymphadenopathy, pruritus, and constitutional symptoms [1, 2]. Rarely, extranodal regions include the spleen, liver, lung, and bone marrow [1]. It is extremely rare to have extranodal involvement of other organs, the central nervous system, or the integument – as in our patient [2-8].

It is known that non-specific skin involvement such as pruritus, hyperpigmentation, urticaria, erythoderma, or acquired ichthyosis occurs fairly commonly, in 17-53 percent [2, 4]. However, these are thought to be paraneoplastic syndromes rather than direct tumor infiltration [2]. Direct tumor involvement is extremely rare and reported in a number of case reports [2, 4, 5, 6, 7, 8]. In 1906, Grosz described the first case of a patient with Hodgkin disease and multiple brownish, "lentil to walnut-sized," ulcerating nodules [2, 4]. Since then, the incidence has been reported to occur in 0.5-3.4 percent of Hodgkin lymphoma patients [2, 4]. Recently, Introcaso et al. have described another case and thoroughly reviewed the literature on cutaneous HL and showed that the number of cases had reportedly diminished over time [4]. It was felt this was likely due to improved treatments and the utilization of stem cell transplantation for relapsed disease [2, 4]. Frequently in cutaneous HL, the presentation is single or multiple dermal or subcutaneous nodules that become ulcerated and involve the skin area over the chest [4, 5, 6]. The mechanism or mechanisms for the skin involvement in HL are not known but postulated to be retrograde lymphatic spread from tumor-involved lymph nodes, direct extension into skin by tumor cells in underlying lymph nodes, or hematogenous spread of the tumor [2, 4].

The diagnosis of classic HL requires careful pathological identification of characteristic binucleated tumor cells (Reed-Sternberg cells), or mononuclear cells (Hodgkin cells) within an inflammatory milieu [1]. These malignant cells represent 0.1-10 percent of all cells in a biopsy, are derived from germinal center B cells in more than 98 percent, and are distributed in a background of reactive cells [1, 3]. Typically, these cells stain positively for CD15 and CD30 but not CD20 [1, 3]. Other than HL, cells resembing Reed-Sternberg cells may be present in other B and T cell lymphomas, carcinomas, melanomas, and sarcomas [1, 3]. In particular, HL must be distinguished from other conditions that present with cutaneous lesions such as mycosis fungoides, granulomatous slack skin disease (CTCL), lymphomatoid papulosis, and anaplastic large cell lymphoma. The latter two may also have CD30 positive cells and require the more specific CD15 positive expression to be differentiated from HL.

Overall, the prognosis in Hodgkin lymphoma is good with greater than an 80 percent five-year survival [1, 3]. However, cutaneous involvement is usually associated with diffuse lymphadenopathy, late stage disease, and poor prognosis [2, 4, 6, 8]. Our case was an exception; the outcome was favorable with a good dermatological response. Rare cases of cutaneous HL with indolent clinical courses have previously been described showing slow progression to generalized lymphadenopathy over years [6, 7]. Thus, it is important to recognize this malignancy, complete the appropriate work-up for staging, and initiate prompt treatment. There are no standardized treatments for Hodgkin lymphoma with skin lesions. Standard treatment is chemotherapy with or without involved field radiation depending on the stage and bulk of the disease [3]. Skin lesions due to Hodgkin lymphoma, as in our case, have been reported to respond to current standard treatment without further therapeutic modalities such as surgical excision, topical therapy, or local cutaneous radiation [2, 4].

Conclusions
Although cutaneous involvement of Hodgkin lymphoma is extremely rare, it merits consideration in the category of atypical causes of non-specific papules, plaques, and ulcers; therefore, enlisting a hematopathologist may be required. Contrary to most reported cases of HL involving skin, our case demonstrates that a good response with adequate therapy is possible.

Acknowledgements: We thank dermatologist Dr. Ronald W. Gottschalk for taking the initial picture. We thank Dr. Barbara Burrall for her constructive review and advice.

Dermatology Online

Denileukin diftitox for the treatment of cutaneous T-cell lymphoma

Denileukin diftitox for the treatment of cutaneous T-cell lymphoma

Biologics. 2008 Dec

Kaminetzky D, Hymes KB.
Division of Hematology/Oncology, New York University School of Medicine, New York, USA.

Cutaneous T-cell lymphoma/mycosis fungoides (CTCL/MF) is a rare lymphoproliferative disorder which can present as an indolent or as an aggressive process involving skin, lymph nodes, and blood. In stages IA, IB and IIA, it is usually managed with topical medications and phototherapy. If there is progression despite application of these treatments, or if the patient presents with a higher stage of disease, systemic chemotherapy or retinoids, rexinoids, biologic response modifiers are often necessary. Consequently, patients are often treated with a sequence of modalities and drugs. Denileukin diftitox (DD, Ontak(R)) is a targeted immunotoxin which has biological activity against malignancies expressing the IL-2 receptor. In addition to its unique mechanism of action, DD has a toxicity profile which does not overlap with most commonly used chemotherapeutic agents. CTCL/MF has been found be particularly susceptible to treatment with this agent. This review will describe the development DD, its proposed mechanism of action, the clinical trials which identified its utility in the treatment of CTCL/MF, the common toxicities encountered with this agent, and the management of these toxicities. In addition the incorporation of DD in the sequential treatment of CTCL/MF and data suggesting potential combination therapies employing this novel agent will be discussed.

Full text article:

DovePress