Primary cutaneous CD30-positive anaplastic large-cell lymphoma of the external auditory canal.

Dec 2012

Marçal N, Campelos S, Dias L, Gonçalves M, Pereira G, Godinho T.

Source

Department of Otorhinolaryngology, Hospital de São Marcos, Sete Fontes, S. Victor 4701-243 Braga, Portugal. nunomarcal.orl@gmail.com.

Abstract

Primary cutaneous T-cell lymphoma is rare. Cutaneous lymphoma is defined as primary when there is an absence of nodal or systemic disease during the first 6 months following diagnosis. We report what we believe to be the first documented case of a primary cutaneous CD30-positive anaplastic large-cell lymphoma of the external auditory canal. The patient was an elderly woman who presented with progressively worsening right otalgia and hypoacusis. Otoscopy revealed an erythematic, ulcerative, nonbleeding, localized lesion in the anterosuperior area of the external auditory canal. The patient underwent an excisional biopsy, and after the diagnosis was established, she underwent 22 sessions of radiotherapy. During follow-up, she exhibited no evidence of recurrence.

PubMed

Cutaneous CD30-positive lymphoproliferative disorders with CD8 expression: a clinicopathologic study of 21 cases.

Nov 2012

Plaza JA, Feldman AL, Magro C.

Source

Department of Dermatopathology, The Medical College of Wisconsin, Milwaukee, WI, USA.

Abstract

Lymphomatoid papulosis (LyP) and cutaneous anaplastic large cell lymphoma (ALCL) belong to the spectrum ofcutaneous CD30+ lymphoproliferative disorders, an indolent form of T-cell lymphoproliferative disease. We reviewed 21 cases of CD30+ lymphoproliferative lesions expressing cytotoxic profile (CD8+). Seven cases of cutaneous ALCL, 2 cases of systemic ALCL involving the skin, and 12 cases of LyP. The cases of LyP were predominated by small lymphocytes exhibiting a prominent epidermotropic pattern consistent with either type B or type D LyP. Four cases showed co-expression of CD56. The ALCL cases included myxoid features, pseudoepitheliomatous change, and an intravascular component. In all cases that were primary in the skin an indolent clinical course was seen while one patient with systemic myxoid ALCL is in remission following systemic multiagent chemotherapy. The paucity of other neutrophils and eosinophils and concomitant granulomatous inflammation were distinctive features in cases of type B and type D LyP. CD30 and CD45 Ro positivity and a clinical course typical of LyP were useful differentiating features from an aggressive cytotoxic CD8+ T cell lymphoma. In all cases that were primary in the skin an indolent clinical course was observed. CD30 and CD45 Ro positivity and a clinical course typical of LyP were useful in preventing a misdiagnosis of an aggressive cytotoxic CD8+ T cell lymphoma.

Wiley OnLine

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

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

Lymphomatoid papulosis in childhood: six case reports and a literature review

Lymphomatoid papulosis in childhood: six case reports and a literature review
Ann Dermatol Venereol. 2008 Oct

Bories N, Thomas L, Phan A, Balme B, Salameire D, Thurot-Guillou C, Dalle S.

Service de dermatologie, hôpital Hôtel-Dieu, 1 place de l'Hôpital, Lyon cedex 02, France.

BACKGROUND: Lymphomatoid papulosis (LyP) is a rare lymphoproliferative disorder. It is now included in the World Health Organisation (WHO) classification of cutaneous lymphomas. Although frequently described in adults, there have been only a few reported cases of LyP in children; diagnosis is often difficult in this population and no clear guidelines have been established regarding management or monitoring. In this article we report six new cases of LyP in children.

PATIENTS AND METHODS: This is a retrospective study of six children, aged between two and 11 years, seen at the Hôtel-Dieu Hospital in Lyon and at the Grenoble Hospital Centre between 2005 and 2008. Each child underwent skin biopsy for histological and immunohistochemical analysis.

RESULTS: All six children presented papulonodular lesions on the limbs and trunk, in some cases necrotic, present for different times and developing in episodes. Histology and immunolabelling announces in all six cases militated in favour of LyP type A, with large CD30+ and CD15- cells dispersed in an inflammatory dermal infiltrate made up for the most part of lymphocytes, polynuclear neutrophils, eosinophils and a small number of histiocytes.

DISCUSSION: Only around 60 cases of LyP have so far been reported in children, principally type A. Association with malignant lymphoma occurs, with high risk in relation to the general population of the same age. Clinical diagnosis is confirmed histopathology and immunolabelling. There is currently no consensus regarding therapeutic management. First-line treatment generally comprises therapeutic abstention or dermal corticosteroids. Methotrexate and phototherapy constitute possible alternatives but should be used only in very disseminate or debilitating forms of the disease.

CONCLUSION: The presentation and course of LyP of childhood differs very little from the adult form. Cases of associated lymphoma have been reported. Although regular clinical monitoring is recommended, there is no call for routine laboratory testing.

EMConsulte