Primary cutaneous aggressive epidermotropic CD8(+) cytotoxic T-cell lymphoma with atypical presentation

Primary cutaneous aggressive epidermotropic CD8(+) cytotoxic T-cell lymphoma is characterized by a proliferation of epidermotropic CD8(+) cytotoxic T cells and an aggressive clinical behavior. Patients present with localized or disseminated eruptive papules, nodules and tumors. We report a case of primary cutaneous aggressive epidermotropic CD8(+) cytotoxic T-cell lymphoma with unusual clinical manifestation. The lesion occurred as multiple brownish macules and flat-topped papules on the hands, feet and face in a 25-year-old woman.     

Cutaneous CD8+ squamous T-cell bullous lymphoma

INTRODUCTION: Bullous forms of cutaneous T-cell lymphomas are rare. A new group of cutaneous T-cell lymphomas has recently been identified as a distinct clinicopathological and immunophenotype entity. These cutaneous T-cell lymphomas express a CD8+ phenotype, rarely expressed in other cutaneous T-cell lymphomas. CASE REPORT: We describe a cutaneous CD8+ squamous T-cell lymphoma with polymorphic clinical features, strongly epidermotropic lymphoid infiltrate and spongiosis, classical for this type of lymphoma. DISCUSSION: Bullous lesions in cutaneous T-cell lymphoma should evoke the possibility of a cutaneous CD8+ T-cell lymphoma, once other bullous diseases have been excluded. Spongiosis, rare in other types of T-cell lymphoma, and strongly epidermotropic pleomorphic lymphoid infiltrate are classical histological features. The association of polymorphic lesions, bullas and atypical CD8+ epidermotropic phenotype should evoke this diagnosis even at the early stage. Treatment is difficult and classical chemotherapy often fails. Prognosis is poor with a mean overall survival of 32 months.     

Primary cutaneous aggressive epidermotropic CD8(+) T-cell lymphoma: Proposed diagnostic criteria and therapeutic evaluation

Primary cutaneous aggressive epidermotropic CD8(+) T-cell lymphoma is a rare cytotoxic lymphoma characterized clinically by aggressive behavior and histologically by prominent epidermotropism of atypical CD8(+) lymphocytes. Despite the continuous addition of new case reports, no definite diagnostic criteria have been established, and an optimum treatment is still awaiting. Herein, we study and analyze the different clinical, histopathological, and immunohistochemical features described in the reported cases. Different therapeutic modalities and their impact on the prognosis of the tumor are also evaluated and presented. We propose two sets of diagnostic criteria. The first comprises constant clinical, histopathological, and immunohistochemical features that are always present in every case, and the combination of which is necessary for the diagnosis. The second set helps to avoid missing cases and includes variable features that may be present in some cases, and to which any emerging finding could be added. Although different therapeutic options have been used, either as single agents or in combinations, there is no standard therapy for primary cutaneous aggressive epidermotropic CD8(+) T-cell lymphoma and the tumor still represents a therapeutic challenge with very poor prognosis.     

Aggressive T cytotoxic CD8+ epidermotropic cutaneous lymphoma: a case in a patient with Steinert's myotonic dystrophy

INTRODUCTION: Primary cutaneous "aggressive" CD8-positive epidermotropic cytotoxic T-cell lymphoma is a rare subset of cutaneous cytotoxic T/NK lymphomas that clearly differs from mycosis fungoides, whether CD4+ or CD8+, by the presence of rapidly evolving tumoral cutaneous lesions, foci of keratinocytes necrosis, a cytotoxic T phenotype and a poor prognosis. CASE REPORT: A 33-year-old man with Steinert's myotonic dystrophy was referred for evaluation of rapidly worsening cutaneous tumors along with marked deterioration of general status. Clinical, histological and immunohistological data led to the diagnosis of primary cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma. CHOP chemotherapy was effective despite cardiac toxicity in the setting of Steinert's dystrophy, but the patient relapsed and died of pulmonary sepsis after chemotherapy was resumed. DISCUSSION: The treatment of primary cutaneous epidermotropic CD8+ cytotoxic T-cell lymphoma is not codified. CHOP chemotherapy is usually the first-line therapy but relapses are frequent with median survival of no more than 34 months. In our patient, an additional difficulty was the cardiac toxicity of cytostatic drugs linked to the myopathy which prevented the use of high dosages, requiring a change of therapeutic regimen.     

Progressive epidermotropic CD8+/CD4- primary cutaneous CD30+ lymphoproliferative disorder in a patient with sarcoidosis

We describe a patient with a CD8+/CD4- primary cutaneous CD30(+) lymphoproliferative disorder with striking epidermotropic histology and coincident cutaneous and systemic sarcoidosis. This patient illustrates the spectrum of clinical and histologic features of CD30+ lymphoproliferative disorders and the need for adequate staging in such cases. This patient's CD30/CD8 coexpression is rare and has clinical and prognostic implications, including mucosally and acrally accentuated lesions and a potentially more aggressive course. Primary cutaneous CD30+ lymphoproliferative disorders have an excellent prognosis; therefore multiagent chemotherapy modalities are generally not indicated. The combination of T-cell lymphoma and sarcoidosis is also rare and may limit treatment options.     

Cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma with aggressive course

BACKGROUND: Cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma is a recently described rare primary cutaneous lymphoma exhibiting aggressive clinical behavior. Only about twenty cases have been described in the literature. Below we report a case involving unusual association of cutaneous vasculitis and lymphoproliferation. CASE REPORT: A 42-year-old senegalese man was hospitalized for cutaneous nodular lesions, which rapidly spread and became necrotic and ulcerated. he had recent weight loss with fever and multiple enlarged lymph nodes. Cutaneous histological analysis showed epidermotropic dermal infiltrate comprising medium and large cd8+ cytotoxic t-cells of unusual angiocentricity with cutaneous vasculitis and fibrinoid necrosis. the patient died 4 months after initiation of treatment with multi-agent chemotherapy. DISCUSSION: This patient presented the characteristics of primary cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma described by Berti. The clinical findings in most cases consist of nodular and ulcerative cutaneous lesions. Histologically, the cutaneous infiltrate is composed of pleomorphic lymphocytes with marked and constant epidermotropism. Immunohistochemistry shows lymphocytes expressing a CD8+ phenotype and cytotoxic proteins, which probably accounts for the local and systemic aggressiveness of the disease, as well as the angiodestructive nature of the infiltrate and the necrotic lesions.     

Indolent CD8-positive T-cell lymphoid proliferation of the ear: a report of two cases

The current classification of primary cutaneous T-cell lymphoma (CTCL) of the World Health Organization (WHO) includes primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma as a provisional entity awaiting cumulative data. Recent reports identify CD3/CD8-positive clonal T-cell lymphoid proliferations arising in the ear and nose that behave indolently and therefore defy currently established subclassification. Here, we report two cases of clonal CD8-positive/granzyme-B-negative T-cell lymphoid proliferations that arose in the ear and behaved indolently. Collectively, these cases suggest that an additional category of cutaneous indolent CD8-positive T-cell lymphoma may be necessary among the existing classification schemes.     

The new World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas: a practical marriage of two giants

Following consensus meetings of the two parent organizations, a new World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification for primary cutaneous lymphomas has recently been published. This important development will now end the ongoing debate as to which of these was the preferred classification. The new classification will facilitate more uniformity in diagnosis, management and treatment of cutaneous lymphomas. In particular, it provides a useful distinction between indolent and more aggressive types of primary cutaneous lymphoma and provides practical advice on preferred management and treatment regimens. This will thereby prevent patients receiving high-grade treatment for low-grade biological disease. This review focuses on those diseases which have found new consensus agreement compared with the original WHO and EORTC classifications. In cutaneous T-cell lymphomas, these include folliculotropic mycosis fungoides, defining features of Sézary syndrome, primary cutaneous CD30+ lymphoproliferative disorders (primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis and borderline lesions) and subcutaneous panniculitis-like T-cell lymphoma. Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma, primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma and cutaneous gamma/delta T-cell lymphoma are allocated provisional entry status and thereby afford better definitions for some cases of currently unspecified primary cutaneous peripheral T-cell lymphoma. In cutaneous B-cell lymphomas, diseases which have found new consensus agreement include primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicular centre lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type and primary cutaneous diffuse large B-cell lymphoma, other. CD4+/CD56+ haematodermic neoplasm (early plasmacytoid dendritic cell leukaemia/lymphoma) now appears as a precursor haematological neoplasm and replaces the previous terminology of blastic NK-cell lymphoma. Other haematopoietic and lymphoid tumours involving the skin, as part of systemic disease, will appear in the forthcoming WHO publication Tumours of the Skin. The new classification raises interesting new problems and questions about primary cutaneous lymphoma and some of these are discussed in this article. It is, however, a splendid signpost indicating the direction in which research in cutaneous lymphoma needs to go. In the interim, we have an international consensus classification which is clinically meaningful.     

Cutaneous natural killer/T-cell lymphoma

Lymphomas are classified as either Hodgkin's or non-Hodgkin's. The 2 subtypes of non-Hodgkin's lymphoma that can present primarily in the skin are cutaneous T-cell lymphoma and cutaneous B-cell lymphoma, both of which tend to be low-grade malignant neoplasms. Recently another distinct subtype of lymphoma was discovered, the natural killer (NK)/T-cell lymphoma, which can involve the skin in a primary or secondary fashion. The NK/T-cell subtype of lymphoma is characterized by the expression of the NK-cell antigen CD56. These CD56(+) lymphomas are further subdivided into nasal NK/T-cell lymphomas that commonly present as midfacial destructive disease and non-nasal NK/T-cell lymphomas that often arise in extranodal locations, including the skin. We report a case of aggressive NK-cell leukemia/lymphoma with numerous secondary cutaneous lesions and review the clinical and histopathologic spectrum of non-nasal CD56(+) lymphomas, with an emphasis on the dermatologic findings.     

Rimming of adipocytes by neoplastic lymphocytes: a histopathologic feature not restricted to subcutaneous T-cell lymphoma

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma of the skin presenting with histopathologic features simulating those of a lobular panniculitis. The presence of neoplastic T-lymphocytes forming a rim around the individual fat cells in the subcutaneous lobules, so-called "rimming" of adipocytes, is considered a characteristic morphologic feature of this type of cutaneous lymphoma. In this study we reviewed a series of 45 biopsy specimens of primary and secondary cutaneous B- and T-cell lymphomas and one of myeloid leukemia involving the subcutaneous tissues and showing rimming of adipocytes (subcutaneous panniculitis-like T-cell lymphoma: n = 16; mycosis fungoides, tumor stage: n = 3; aggressive epidermotropic CD8(+) T-cell lymphoma: n = 2; cutaneous gamma/delta T-cell lymphoma: n = 4; extranodal NK/T-cell lymphoma, nasal type: n = 4; cutaneous medium-large pleomorphic T-cell lymphoma, NOS: n = 5; CD4(+)/CD56(+) hematodermic neoplasm (blastic NK-cell lymphoma): n = 7; secondary cutaneous large B-cell lymphoma: n = 3; secondary cutaneous lymphoplasmacytic lymphoma: n = 1; specific cutaneous manifestations of acute myelogenous leukemia: n = 1). We could demonstrate that rimming of adipocytes by neoplastic cells can be recognized not only in subcutaneous panniculitis-like T-cell lymphoma, but also in several different entities of malignant lymphoma with skin involvement. Precise classification of cases with prominent involvement of the subcutaneous tissues can only be achieved upon precise correlation of clinicopathologic and phenotypic features. Rimming of adipocytes should not be considered specific of subcutaneous panniculitis-like T-cell lymphoma.     

CD56+ lymphoma with skin involvement: clinicopathologic features and classification

BACKGROUND: Extranodal lymphomas expressing CD56 (neuronal cell adhesion molecule) are characterized by a high incidence of cutaneous involvement and a very aggressive clinical course. Knowledge about the prognosis and clinicopathologic features of CD56(+) lymphomas with skin involvement is very limited. OBJECTIVES: To determine survival and prognostic factors for extranodal CD56(+) lymphomas with skin involvement and to describe their clinicopathologic features. DESIGN: Retrospective literature survey and case studies. PATIENTS: A total of 181 patients with CD56(+) lymphoma involving the skin: 177 cases from the literature and 4 new cases. MAIN OUTCOME MEASURE: Survival and its dependence on the following putative prognostic factors: staging, histopathologic findings, lymphocyte markers, T-cell receptor gene rearrangement, Epstein-Barr virus infection, treatment modality. RESULTS: Three major subtypes of CD56(+) lymphoma in the skin were distinguished: blastic lymphoma, nasal-type natural killer-cell/T-cell lymphoma, and subcutaneous panniculitislike lymphoma. The disease disseminated readily, mainly to lymph nodes, bone marrow, the central nervous system, and the liver, but 45% of patients had a purely cutaneous disease at presentation. All subtypes had a very aggressive course with a median survival of 14 months. The main risk factors were age older than 55 years (hazard ratio [HR], 2.5; 95% confidence interval [CI], 1.8-3.2), systemic dissemination at presentation (HR, 2.0; 95% CI, 1.5-3.3), and lack of CD30 (HR, 3.8; 95% CI, 1.4-4.9) or CD4 expression (HR, 1.56; 95% CI, 1.06-2.57). The different treatment modalities did not improve survival. CONCLUSIONS: CD56(+) lymphomas involving the skin are rare and extremely aggressive regardless of their histologic presentation and the extent of skin involvement. No effective treatment is available. The risk of death is particularly increased in older patients with CD30(-)CD4(-) lymphomas.     

Fatal CD8+ epidermotropic cytotoxic primary cutaneous T-cell lymphoma with multiorgan involvement

A 70-year-old woman presented with a 3-month history of two ulcerated erythematous-violaceous nodular lesions over the nose and forehead, respectively. The patient's history included a similar cutaneous nodule on the glabella diagnosed as pseudolymphoma 2 years ago.At that time, despite the diagnosis of a benign disease, an adequate staging was performed, ruling out any extracutaneous involvement. During hospitalization, multiple purpuric papules developed over the abdomen, and the disease spread to mediastinal lymph nodes, lungs and the central nervous system. Based on the histologic, immunophenotypic and molecular biology findings, a diagnosis of CD8+ epidermotropic cytotoxic primary cutaneous T-cell lymphoma was made. Secondary skin involvement by a CD8+ extracutaneous T-cell lymphoma could not be excluded with certainty, but seemed to be unlikely because of the negativity of the initial workup. The patient died from complications of right femoral artery thrombosis before starting specific polychemotherapy 21 months after onset of the disease. Among primary cutaneous T-cell lymphomas, the CD8+ epidermotropic cytotoxic subset comprises rare, highly aggressive forms characterized by metastatic spread to unusual sites such as the oral cavity, lungs, testis and the central nervous system but usually not to the lymph nodes. These cases seem to be distinct from mycosis fungoides with CD8+ phenotype, which shows a nonaggressive clinical behavior.     

Primary cutaneous aggressive epidermotropic CD8+ T cell lymphoma with a chronic and indolent course. Is this different from peripheral T cell lymphoma?

Cutaneous T cell lymphomas most commonly have a CD4+ memory T cell phenotype and exhibit a relatively indolent course, but may in rare cases present with a CD8+ cytotoxic phenotype with a strikingly more aggressive clinical behavior. Primary cutaneous aggressive epidermotropic CD8+ T cell lymphoma is an extremely rare entity with distinct clinicopatological features. The clinical features and prognosis of the recently-described CD8+ peripheral lymphoma are very different from cytotoxic CD8+ epidermotropic lymphoma, but the histological and phenotypic characteristics are very similar. We report a new case of CD8+ epidermotropic lymphoma with a chronic course and suggest the possibility of an overlap between these two types of lymphoma.     

Primary cutaneous CD8+ cytotoxic T‐cell lymphoma involving the epidermis and subcutis in a young child

CD8+ cytotoxic T‐cell lymphoma involving the skin represents a heterogeneous group of diseases that include subcutaneous panniculitis‐like T‐cell lymphoma, primary cutaneous aggressive epidermotropic CD8+ cytotoxic T‐cell lymphoma, and ‘type D’ lymphomatoid papulosis. In this report, we describe a case of CD8+ cytotoxic T‐cell lymphoma involving both the epidermis and subcutis. The patient was a 6‐year‐old girl who presented with a 3‐year history of multiple plaques on her trunk and legs. The lesions had relapsed twice but responded well to prednisone. Histopathologic examination showed the proliferation of atypical lymphocytes in the epidermis, dermis and subcutaneous tissue. On immunohistochemical analysis, the atypical lymphocytes were positive for βF1, CD3, CD8, perforin, granzyme B and TIA‐1, but negative for T‐cell receptor (TCR) γ, CD4, CD30 and CD56. It was difficult to classify this tumor in terms of the known types of cutaneous lymphoma, and this case should be differentiated with subcutaneous panniculitis‐like T‐cell lymphoma and primary cutaneous aggressive epidermotropic CD8+ T‐cell lymphoma.     

Primary cutaneous acral CD8+ T‐cell lymphoma of the ear: A case report

Primary cutaneous acral CD8+ T‐cell lymphoma (TCL) is a rare, distinct type of cutaneous TCL. Despite its worrisome histological appearance it has a benign clinical course. It is therefore important to recognize this as a distinct entity from other more aggressive CD8+ lymphomas, for which the management is very different.     

Epidermotropic CD8+ cytotoxic T-cell lymphoma exhibiting a transition from the indolent to the aggressive phase, accompanied by emergence of CD7+ cells and formation of neutrophilic pustules

A 47-year-old-man presented with rashes on his trunk and limbs, and a diagnosis of parapsoriasis was made. Ten years later, the rashes had progressed gradually to form plaques and tumours. Gene rearrangement studies revealed monoclonality of the T-cell receptor β-chain (TCR-Jβ)1 gene, and results of flow cytometry and immunohistochemical examination confirmed a diagnosis of epidermotropic CD8+ cytotoxic T-cell lymphoma. The clinical course of the disease remained indolent for some time, but about 2 years later, neutrophilic pustules formed on the surface of the skin lesions, and tumours developed in the patient's testes. Using flow cytometry, emergence of CD7+ cells was found. The patient died the following year of respiratory failure due to brain herniation. On postmortem examination, CD8+ tumour cells were found in the brain. This case demonstrates an unusually protracted indolent phase in a patient with cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma; its transition into the aggressive phase was accompanied by emergence of CD7+ cells and formation of neutrophilic pustules.     

A Case of Aggressive NK/T-cell Lymphoma/Leukemia with Cutaneous Involvement in Adolescence

NK/T-cell lymphoma (NKTCL) is characterized by the expression of the NK-cell antigen CD56. Non-nasal NK/T-cell lymphomas are subdivided into primary cutaneous and 4 subtypes of secondary cutaneous lymphomas; nasal type, aggressive, blastic (blastoid), and other specific NK-like cell lymphoma. Aggressive NK/T-cell lymphoma/leukemia is a rare leukemic variant of nasal type NKTCL. We herein report a rare case of aggressive NK/T-cell lymphoma/leukemia with cutaneous involvement in adolescence.     

多脏器累及的亲表皮CD8~+ T细胞淋巴瘤1例

患者男,46岁,全身渗出性红斑、头皮脓肿9月。入院检查发现累及肺、肝脏,皮肤组织病理示:表皮海绵水肿,真皮弥漫淋巴细胞,异型细胞具亲表皮性,免疫组化示:LCA(+),CD8(+),TIA(+),TCR基因重排阳性,诊断:亲表皮CD8+皮肤T细胞淋巴瘤。予以2次CHOP化疗,无效死亡。本病在国内首次报道,具有独特临床病理特点,早期累及皮外,侵袭性高,无有效治疗方法,预后差。     

CD56-positive cutaneous lymphoma: a poorly recognized entity in the spectrum of primary cutaneous disease

CD56-positive (CD56+) lymphomas, characterized by the expression of the neural cell adhesion molecule on pathological lymphocytes, share a frequent extranodal involvement and a generally aggressive course. Five CD3- CD56+ lymphoma patients presenting with nodular lesions were identified among 180 immunophenotyped cutaneous lymphomas. All the patients were men, with ages ranging from 55 to 78 years. After staging, two patients were diagnosed as having primary cutaneous lymphomas: the remaining three had the secondary cutaneous type. The clinical course was aggressive and four patients died within 8 months from diagnosis. The remaining patient is still alive after a 17-month follow-up. The histological diagnosis was immunoblastic lymphoma in two patients, and medium and large cell pleomorphic lymphoma in three. The angiocentric infiltrate was located mainly in the dermis: azurophilic granules were present in three of the five patients. Immunogenotypic analyses suggested the natural killer cell origin of these neoplasias: all cases exhibited a CD56+ CD3- CD5- T-cell receptor (TCR) silent phenotype, and Southern blot analysis showed a germline configuration of the TCR β-chain gene.