Mycosis fungoides and chronic lymphocytic leukaemia--composite T-cell and B-cell lymphomas presenting in the skin

Composite lymphomas involving cutaneous B-cell and T-cell lymphomas are very uncommon. We report here the unique circumstance of a patient with mycosis fungoides (primary cutaneous T-cell lymphoma) who later developed chronic lymphocytic leukaemia (B-cell lymphoproliferation, B-CLL), which presented in the skin (leukaemia cutis) as a composite lymphoma affecting an earlobe. The presence of both lymphoproliferative disorders was confirmed with immunophenotyping and the finding of both immunoglobulin gene rearrangements and T-cell receptor gene rearrangements in the ear and the same T-cell receptor gene rearrangement in a plaque lesion of mycosis fungoides on the arm.     

Cutaneous graft-versus-host-like reaction in systemic T-cell lymphoma

We report a case of systemic T-cell lymphoma with cutaneous lesions showing histological features of a cutaneous graft-versus-host-like-reaction. Histology from liver, lymph node and bone marrow showed a malignant T-cell infiltrate. T-cell receptor gene rearrangement studies confirmed the diagnosis. A cutaneous graft-versus-host-like reaction has been reported with disseminated malignancy and one case has been reported with systemic lymphoma. Graft-versus-host disease normally occurs when lymphocytes from an immunocompetent donor are introduced into a histo-incompatible recipient who is incapable of rejecting them. In our patient a similar reaction may have occurred if the lymphoma was composed of cytotoxic cells or if a cell-mediated immune response against the malignant T-cells cross-reacted with epidermal keratinocytes. Alternatively the malignant T-cells could have been functionally active and induced a lichenoid reaction in the skin.     

Dual genotype in cutaneous T cell lymphoma: immunoglobulin gene rearrangement in clonal T cell malignancy

Genomic DNA digests of peripheral blood lymphocytes from 13 patients with the leukemic phase of the T cell neoplasm cutaneous T cell lymphoma were studied by hydridization using probes for the constant region of the beta chain of the T cell receptor, the joining region of the immunoglobulin heavy chain gene, and the kappa and lambda light chain genes. Lymphocytes from all 13 cutaneous T cell lymphoma patients contained DNA with clonal rearrangements of the beta chain gene of the T cell receptor. In addition, DNA from 4 patients contained an immunoglobulin gene rearrangement. T cell enrichment studies of peripheral blood lymphocytes from 2 patients confirmed that the immunoglobulin gene joining region rearrangement was confined to the T cell population. These results demonstrate that cutaneous T cell lymphoma is a clonal T cell malignancy that frequently expresses a dual genotype. A multiparameter approach, including DNA probes for the beta chain of the T cell receptor, as well as the immunoglobulin genes, immunophenotyping, and cytogenetics, is valuable in the diagnosis of cutaneous T cell lymphoma.     

Cutaneous composite lymphoma of mycosis fungoides and Hodgkin lymphoma: Response to sequential therapy

Composite lymphoma is defined as two or more morphologically and immunophenotypically distinct lymphoma clones that occur in the same tissue site. The occurrence of cutaneous composite lymphoma (CCL) is extremely rare. Here we report a unique case of CCL consisting of Hodgkin lymphoma (HL) and mycosis fungoides (MF). Our patient presented with longstanding erythematous plaques on the skin and later developed axillary lymph node enlargement. Histopathologically, the skin lesions were characterized by a dense dermal lymphocytic infiltrate with prominent epidermotropism of pleomorphic T-cells, consistent with typical MF. Nonetheless, scattered large atypical cells resembling Reed-Sternberg (R-S) cells were interspersed among these atypical T-cells in the deep dermis. Immunophenotyping suggested a HL origin of these R-S cells. Monoclonality of T-cell receptor beta gene was detected in the skin, monoclonal immunoglobulin heavy chain gene rearrangement was identified in these R-S cells microdissected from the deep dermis, confirming the origin from HL. The lymph node biopsy showed nodular sclerosis classic Hodgkin lymphoma. Therefore, CCL of HL and MF, with lymph node HL was diagnosed. The lesions of this patient responded to a sequential treatment to HL and MF. Being aware of this rare CCL facilitates correct diagnosis and proper clinical management.     

Examination of HTLV-I integration in the skin lesions of various types of adult T-cell leukemia (ATL): independence of cutaneous-type ATL confirmed by Southern blot analysis

The various clinical features of adult T-cell leukemia/lymphoma (ATL) are frequently accompanied by skin eruptions. Recently, a cutaneous type of ATL has been proposed by clinical studies. We analyzed the viral integration of human T-cell leukemia virus-I (HTLV-I) and monoclonal rearrangement of T-cell receptor (TCR) gene in blood lymphocytes and the cutaneous infiltrated cells of nine ATL patients with various clinical features and skin eruptions. We classified them by the results of Southern blot analysis and propose a cutaneous-type ATL accordingly. In two of them, we could detect the monoclonal integration of HTLV-I and T-cell monoclonality only in the skin but not in the peripheral lymphocytes. We also demonstrated the time course study in one patient. Clinicians should be aware of the HTLV-I positive cutaneous T cell lymphoma that can be named cutaneous-type ATL. Examination of viral integration and T-cell monoclonality in skin lesions is required to make an exact diagnosis of cutaneous ATL.     

Angiocentric primary cutaneous T-cell-rich B-cell lymphoma: a case report and review of the literature

BACKGROUND: T-cell-rich B-cell lymphoma (TCRBCL) is an uncommon B-cell lymphoma, which is characterized histologically by a small number of neoplastic B cells surrounded by large numbers of nonneoplastic T cells. Diagnosis is frequently difficult because the neoplastic 'B-cell population may be quite sparse, and immunohistochemical and molecular analysis to identify the B-cell origin and clonality of the cells is necessary. METHODS: In this report we present an additional case of primary cutaneous TCRBCL with immunohistochemical and gene rearrangement studies and review the literature of this unusual entity. RESULTS: The patient was a 52-year-old woman who had a slowly growing cutaneous lymphoma which fulfills the strictest criteria initially proposed for a diagnosis of TCRBCL. This case has additional features of a prominent angiocentric/angioinvasive histology and dual clonality, showing both immunoglobulin heavy chain and T-cell receptor gene rearrangements. CONCLUSIONS: Controversy surrounds the notion of TCRBCL as a distinct clinicopathological entity. There have only been 14 reported cases of TCRBCL with skin involvement in the literature and only seven of these cases have arisen in the skin. To better understand the histological and clinical characterisitcs of TCRBCL we have reviewed previously reported cases of TCRBCL with skin involvement, and contrast them with the present case.     

Sodium valproate-induced cutaneous pseudolymphoma followed by recurrence with carbamazepine

We report a patient with a sodium valproate-induced cutaneous pseudolymphoma, presenting with an erythematous papule, histologically mimicking a non-epidermotropic T-cell lymphoma. Polymerase chain reaction study of the skin biopsy revealed monoclonal rearrangement of the T-cell receptor gamma gene. Withdrawal of sodium valproate was followed by regression of the lesion, but 5 months after substitution by carbamazepine, two further papules appeared, with similar histological features and a T-cell clone identical to the initial one. Carbamazepine was stopped and the lesions disappeared without relapse over a 4-year follow-up. Sodium valproate is very rarely responsible for a hypersensitivity syndrome, and our case is the first report of sodium valproate-induced cutaneous pseudolymphoma. The recurrence with carbamazepine may be due to a common effect on T-cell lymphocyte function. The return of the same monoclonal population shows that the recurrence of monoclonal T cells may be observed in benign conditions and is not an exclusive hallmark of cutaneous lymphoma.     

Cutaneous involvement in the lymphoepithelioid variant of peripheral T-cell lymphoma, unspecified (Lennert lymphoma). Report of a case and review of the literature

Lennert lymphoma (LL), or the lymphoepithelioid variant of peripheral T-cell lymphoma, is an uncommon entity with rarely seen or reported presentations in the skin. Cutaneous involvement of LL has been characterized by asymptomatic, non-ulcerated, red to violet papules, nodules and small plaques (less than 5 cm) on the trunk and extremities. Histologically, there are localized cellular lymphoid infiltrates in the dermis that tend to localize around blood vessels or skin appendages. Key to the diagnosis of LL is the presence of epithelioid histiocytes and atypical small lymphoid cells without increased vascularity or epidermotropism. Immunophenotyping shows a dense monoclonal T-cell population commonly associated with aberrant loss of T-cell-associated antigens. T-cell receptor gene rearrangements are also identified. Patients typically present with advanced stage and have a low 5-year survival. Herein, we present a case of cutaneous involvement by LL at the time of initial presentation that persisted after initiation of chemotherapy and was finally verified as secondary cutaneous involvement of LL 1 year later histologically, immunophenotypically and by T-cell receptor gene rearrangement studies.     

T-cell-rich B-cell lymphoma presenting in skin

We reviewed our experience with six T-cell-rich B-cell lymphomas (TRBL) presenting in skin. Immunohistochemical studies were performed on all biopsies. The lymphoid population consisted mainly of CDS and/or UCHL-1 (CD45RO) positive T cells. 5 to 15% of the lymphoid cells stained for the B-cell marker L26 (CD20). Monoclonality of the B-cell component was demonstrated in all cases, utilizing either light chain restriction (5 cases) or clonal immunoglobulin heavy chain gene rearrangement by polymerase chain reaction (PCR) (2 cases). One case was confirmed to be monoclonal by both techniques. Additionally, no clonal rearrangements of the T-cell receptor gamma gene were observed. There was considerable morphological variety in these cases. In H&E stained sections, the differential diagnosis included pseudolymphoma, peripheral T-cell lymphoma, Hodgkin's disease, Lennert's lymphoma and a MALT lymphoma. A significant component of monoclonal plasma cells was present in 3 of 6 cases, suggesting a possible origin from cutaneous immunocytoma. In fact, one of our cases was a biphasic lymphoma displaying TRBL with a small focus of immunocytoma. We conclude that immunophenotypic analysis is necessary for the diagnosis of TRBL. Pathologists should be aware of this type of cutaneous B-cell lymphoma to avoid misinterpretation as a pseudolymphoma.     

Blastic natural killer cell and extranodal natural killer cell-like T-cell lymphoma presenting in the skin: report of six cases from the UK

BACKGROUND: Some lymphomas express natural killer (NK)-cell markers such as the neural cell adhesion molecule, which is recognized by the CD56 antibody. These lymphomas may present in the skin, but do not represent a homogeneous group. The new World Health Organization classification of lymphoma/leukaemia recognizes several types of NK/T-cell neoplasm, including blastic NK-cell lymphoma, which characteristically presents with cutaneous lesions. OBJECTIVES: To describe the clinical, pathological and molecular features in six cases of CD56+ lymphoma with cutaneous presentation. METHODS: The clinical, histopathological and immunophenotypic features of six patients were reviewed. In addition, in situ hybridization (ISH) to identify Epstein-Barr virus (EBV) mRNA, and polymerase chain reaction analysis to identify the presence of a clonal population of T cells or B cells were performed on lesional skin. RESULTS: All patients presented with widespread nodules and plaques, which in five cases were a characteristic purple colour. Four patients developed disseminated disease, three with neurological involvement. These four patients died between 14 and 46 months following diagnosis (median 30 months). In four of six cases the histopathological and immunohistological features were in keeping with a blastic NK-cell lymphoma. No clonal immunoglobulin heavy chain (IgH) or T-cell receptor (TCR) gene rearrangement was detected in the four cases consistent with an origin from NK cells. A further case fitted the criteria for an extranodal NK/T-cell lymphoma of nasal type and was also the only case to show evidence of EBV mRNA by ISH. A clonal T-cell population was identified in the final case. This patient also exhibited molecular evidence of a clonal B-cell population and a t(14;18) translocation confirmed by sequence analysis. CONCLUSIONS: Our data confirm that NK-cell lymphomas presenting in the skin are a heterogeneous group, and that in the U.K., blastic NK-cell lymphoma is more common than extranodal NK/T-cell lymphoma of nasal type. These lymphomas pursue an aggressive course, with rapid development of disseminated disease, and resistance to chemotherapy. Detailed immunophenotyping is needed to distinguish the different types. Our molecular data indicate that blastic NK-cell lymphoma cases lack clonal TCR/IgH gene rearrangements consistent with an NK-cell origin. Our ISH findings indicate that EBV plays a pathogenetic role only in extranodal NK/T-cell lymphoma of nasal type.     

Cutaneous peripheral T-cell lymphoma of cytotoxic phenotype mimicking extranodal NK/T-cell lymphoma

Cutaneous peripheral T-cell lymphoma unspecified is a rare neoplasm that is infrequently associated with Epstein-Barr virus (EBV) infection. In contrast, extranodal natural killer (NK)/T-cell lymphoma, although also rare, is known to be strongly associated with EBV and occurs most commonly in the nasal region. We report the case of a 55-year-old male who presented with fever and an indurated cutaneous plaque with ulceration. This cutaneous neoplasm showed diffuse dermal lymphomatous infiltration and tumor necrosis, with neoplastic cells expressing CD2, cytoplasmic CD3 (CD3ε), CD8, CD16, CD30, T-cell intracellular antigen-1, and granzyme B but not CD56, BF1, or T-cell receptor (TCR) δ1. Furthermore, the tumor cells were noted to be diffusely positive for EBV by in situ hybridization. A monoclonal TCR gene rearrangement was demonstrated. The disease showed an aggressive clinical course, and the patient died within 3 weeks of diagnosis without complete staging or chemotherapy. According to the 2005 World Health Organization/European Organization for Research and Treatment of Cancer scheme for cutaneous lymphoma and the 2008 WHO classification for lymphoid neoplasms, our case would have been classified as a nasal type extranodal NK/T-cell lymphoma with T-cell lineage. However, the expressions of CD8 and CD16, in addition to a monoclonal TCR gene rearrangement, are unusual findings in NK/T-cell lymphoma, and we believe such a phenotype/genotype should be more appropriately classified as an EBV-positive peripheral T-cell lymphoma, unspecified with a cytotoxic phenotype. Detailed clinicopathologic and molecular studies of similar cases may shed light on the prognostic impact of NK vs. T-cell lineage on extranodal NK/T-cell lymphomas.     

Cutaneous non-epidermotropic lymphoma associated with human immunodeficiency virus infection

A case of pure non-epidermotropic cutaneous lymphoma in a human immunodeficiency virus-infected patient is reported following a viral opportunistic infection [cyto-megalovirus (CMV) hepatitis]. The lymphoid infiltrate was Epstein–Barr virus and CMV negative with a CD30-positive T-cell phenotype. Molecular analysis demonstrated T cell receptor gene rearrangement, but a non-aggressive disease course was noted supporting a cautious therapeutic approach in this case.     

CD13 and TCR clone: markers of early mycosis fungoides

Making a differential diagnosis between early mycosis fungoides and parapsoriasis is often difficult at the clinical and histological level. The aim of this study was to explore markers that could help in this process. A total of 88 patients were included in 2 categories: large plaque parapsoriasis and digitiform parapsoriasis. A histological examination was performed for each patient, and expression of the antigen My7 (CD13), which is lacking in cutaneous T-lymphomas (but not in inflammatory lesions) and rearrangement of the T-cell receptor gene were analysed. A histological aspect of epidermotropic cutaneous T-cell lymphoma was observed in 23.5% of cases of large plaque parapsoriasis and 15% of cases of digitiform parapsoriasis. A disappearance of My7 antigen was noted in the 2 forms of parapsoriasis, more frequently when there was cutaneous T-cell lymphoma histology. A cutaneous clone was observed in 10.3% of cases of large plaque parapsoriasis, but not of digitiform parapsoriasis. For 3 patients, a cutaneous clone and a disappearance of My7 were associated with a non-specific histology. Considering these histological, immunological and molecular biological data, it appears that My7 antigen combined with T-cell clone may help the dermatologist to confirm the diagnosis of early mycosis fungoides. Moreover, further studies will determine whether CD13 is an early prognostic marker of evolution of a parapsoriasis to mycosis fungoides. Finally, these results demonstrate that digitiform parapsoriasis can be an early stage of MF.     

T-cell receptor and immunoglobulin gene rearrangements in cutaneous T-cell-rich pseudolymphomas

T-cell rich, small lymphoid infiltrates of the skin may cause considerable problems in the differential diagnosis of reactive versus neoplastic lymphoproliferations, particularly when they lack the morphologic and immunophenotypical criteria for a malignant lymphoma. We did histologic, immunohistologic, and gene rearrangement studies on 10 biopsies from patients with persistent nodular T-cell-rich skin lesions refractory to topical therapy. Based on clinical and immunohistochemical findings, no discrimination was possible between reactive lesions and malignant lymphoproliferations. Histologically, most of the cases contained T-lymphocytic infiltrations that were assumed to be reactive; however, in four biopsies a neoplastic infiltration could not be excluded. Although the T-cell receptor (TCR) beta chain and the immunoglobulin heavy chain (IgH) genes were in germ-line configuration in nine of 10 cases, indicating a predominantly polyclonal lymphocellular infiltrate, in one patient without clinical evidence of malignant lymphoma at presentation a clonally rearranged TCR beta chain gene with the IgH gene in germ-line configuration was detected. One year later, the patient developed a cutaneous pleomorphic T-cell lymphoma and subsequently a large cell anaplastic (CD30+) T-cell lymphoma in an inguinal lymph node. We conclude that clonal T-cell proliferations can be detected by molecular genetic analysis of T-cell-rich, small lymphoid infiltrates of the skin. This finding may precede development of an overt malignant T-cell lymphoma.     

Syringotropic and pilotropic cutaneous T-cell lymphoma without follicular mucinosis

BACKGROUND: Mycosis fongoides rarely exhibits predilection for infiltration of hair follicles and eccrine glands. We report the case of a patient with cutaneous T-cell lymphoma with syringotropism and pilotropism without follicular mucinosis. CASE REPORT: A 51-year-old man presented with erythematous infiltrated patches with alopecia and anhydrosis, cystic lesions, comedon-like lesions, follicular keratosis and an ulcer over the lower left leg. Clinical examination revealed no palpable adenopathy or hepatosplenomegaly. The patient complained about hypohydrosis. Histological examination of skin biopsies evidenced pilotropic cutaneous T-cell lymphoma without follicular mucinosis. Immunohistological examination and T-cell receptor B-chain gene rearrangement analysis showed a clonal population of T-cells. Moreover sweat glands and sweat ducts were infiltrated by atypical lymphocytes with syringolymphoid hyperplasia. DISCUSSION: Syringolymphoid hyperplasia and folliculotropism without follicular mucinosis are rarely seen in mycosis fongoides. Deep biopsies of adnexal structures are required for this critical diagnosis and clonal rearrangement of TCR genes is a reliable means of assessing clonality. Syringolymphoid hyperplasia and pilotropism without mucinosis are variants of cutaneous T-cell lymphomas.     

Cutaneous lymphoid hyperplasia and other lymphoid infiltrates of the breast nipple: a retrospective clinicopathologic study of fifty-six patients

This study characterizes the clinicopathological spectrum of lymphoproliferations involving the breast nipple and/or areola. Morphologic, immunohistochemical, molecular-genetic, and clinical features of 58 specimens from 56 patients were analyzed. They were re-diagnosed as cutaneous lymphoid hyperplasia (CLH, n = 44); other benign lymphoid infiltrates (OBLI, n = 8); peripheral T-cell lymphoma, not otherwise specified (n = 1); cases with overlapping features of CLH and B-cell lymphoma (n = 3), one of them composed of spindle cells. Cutaneous lymphoid hyperplasia infiltrates were dense, composed mainly of B cells forming follicles with germinal centers (GC). Cutaneous lymphoid hyperplasia frequently showed features suggesting a malignancy as coalescing follicles with non-polarized germinal centers lacking mantle zones, and smudged infiltrates of lymphoid cells spreading into collagen (often as "Indian files"), smooth muscle, vessel walls, and nerve sheaths. Only two cutaneous lymphoid hyperplasias recurred; otherwise all patients are without disease (mean follow-up 62 months). Monoclonal rearrangement of immunoglobulin heavy chain gene was detected in five, and of T-cell receptor gamma gene in two cutaneous lymphoid hyperplasias using polymerase chain reaction (PCR), but the patients fared well too. In 47% of cases Borrelia burgdorferi was detected by polymerase chain reaction and/or serology, of which one was monoclonal. We conclude that cutaneous lymphoid hyperplasia is the most common lymphoproliferation of the breast nipple, rarely recognized clinically, and often overdiagnosed histologically as lymphoma.     

A rare case of the cutaneous form of adult T-cell leukaemia/lymphoma: assessment of remission by PCR for clonal T-cell receptor gamma gene rearrangements in an electron beam-irradiated cutaneous lesion

Adult T-cell leukaemia/lymphoma is a lymphoproliferative disorder aetiologically associated with human T-cell lymphotropic virus type I infection. A cutaneous lesion often develops in the disease, and in rare cases, is even the only manifestation. Here we report a rare case of 'cutaneous' adult T-cell leukaemia/lymphoma with neither atypical cells in the peripheral blood nor lymph node involvement. All nodular lesions were completely eliminated after local electron beam irradiation (20 Gy/nodule in total). To evaluate whether or not there were residual lymphoma cells in the skin, we performed PCR to detect clonal T cell receptor gamma gene rearrangements. The sample from the nodule before irradiation showed evidence of a rearranged band, which was not detected at the same site after treatment nor in any peripheral blood. The findings suggest that this procedure is useful for the evaluation of therapeutic effects and the early detection of lymphoma recurrence.     

A clonal CD4-positive T-cell line established from the blood of a patient with Sézary syndrome

The reported inability to establish long-term T-cell lines from the blood of cutaneous T-cell lymphoma patients with circulating neoplastic T cells has hindered the development of an in vitro system to investigate Sézary syndrome. We have established a rapidly proliferating T-cell line from the peripheral blood of a patient with Sézary syndrome, which expresses a mature helper T-cell phenotype and contains cytogenetic abnormalities and T-cell receptor gene rearrangements identical to those in the patient's blood. The method of establishment and characteristics of this line are described.