CCR4 Expression by atypical T cells in systemic pilotropic lymphoma: its behavior under treatment with interferon gamma, topical PUVA and systemic retinoid

We describe an 88-year-old Japanese patient with pilotropic T cell lymphoma involving the peripheral blood as well as lymph nodes. This patient presented with multiple red follicular papules, confluent, infiltrated erythematous plaques and nodules. Moreover, he was conspicuous for the presence of total alopecia of the scalp and eyebrows. Histopathologically, the lesional skin showed dense follicular and perifollicular infiltrates of atypical lymphocytes. The flow cytometry disclosed the presence of weakly CD4+ CCR4+ cell populations that would not be detected in the peripheral blood from healthy controls. The patient responded well to topical PUVA and systemic etretinate (retinoid-PUVA) and intravenous IFN-gamma. Parallel with the decrease in atypical cells in the peripheral blood, the percentage of weakly CD4+ CCR4+ T cells declined. However, about 1 week after we discontinued this treatment because of the side effects, the lymph node swelling became prominent, and, 4 weeks later, the patient died before restarting any specific chemotherapy.     

T cells in cutaneous lesions of Sézary syndrome and T-cell leukemia. Characterization by monoclonal antibodies

Anti-T-cell monoclonal antibodies (LEU series) immunoperoxidase technique study for the presence of T cells in cutaneous lesions from four patients with Sézary syndrome and one patient with chronic T-cell leukemia showed that most dermal-lymphoid cells from three patients with Sézary syndrome were reactive with monoclonal antibodies to anti-pan T-cell (LEU-1) and helper T-cell (LEU-3a) subsets but not with those to suppressor-cytotoxic T-cell (LEU-2a) subsets. One patient with progressive disease had atypical dermal-lymphoid cells positive for pan T-cell (LEU-1). Epidermotropic cells were reactive to LEU-1 in all four patients, LEU-2a in one patient, and LEU-3a in one patient. Neoplastic cells in skin lesions of chronic T-cell leukemia showed strong positive staining with LEU-1, but were reactive with both anti-T-cell subset, monoclonal antibodies. The atypical, dermal-lymphoid cells in Sézary syndrome represent mature, helper T cells in most cases. The absence of T-cell subset antigens in one patient with fulminant Sézary syndrome and the finding of both T-cell subset antigens on T-cell leukemia cells suggest the presence of actively proliferating, immature T cells in those cases.     

Characterization of benign cutaneous lymphocytic infiltrates by monoclonal antibodies

Skin biopsies from nine patients with a histological and/or clinical diagnosis of cutaneous lymphocytoma, lymphoplasia or Jessner's lymphocytic infiltrate were examined by immunoenzymatic labelling with a panel of monoclonal antibodies against lymphocytes and accessory cells. Similar cellular constituents were demonstrated in the biopsies from three patients with lymphocytoma, two with lymphoplasia and two with atypical lymphocytes, but a protracted benign clinical course. The infiltrates from these patients consisted of T cells, Langerhans cells, related HLA-DR positive dendritic dermal cells and clusters of polyclonal B cells. In four patients, the B cell clusters contained B cell accessory follicular dendritic cells, and thereby closely resembled the B cell follicles seen in lymphoid organs. The T cells were predominantly T helper/inducer cells and in all patients the T cells expressed HLA-DR. One patient diagnosed as lymphocytoma cutis differed from the other patients by having no detectable B cells. One patient with Jessner's lymphocytic infiltrate differed from the other patients by having a marked relative predominance of T suppressor/cytotoxic cells. These data suggest that cutaneous lymphocytoma and lymphoplasia are basically similar disorders which may be considered to be exaggerated immune responses, whereas Jessner's lymphocytic infiltrate may be a separate entity. Immunological analysis may assist in establishing a definite diagnosis in cases of lymphocytoma or lymphoplasia with atypical cytological features.     

CD30 positive anaplastic large‐cell lymphoma mimicking Langerhans cell histiocytosis

The presence of CD 1a+ dendritic cells (DC) has been well described in T‐cell lymphoproliferative disorders, and the presence of large numbers of DCs has rarely been reported as a mimicker of Langerhans cell histiocytsis (LCH). We present the case of a 56‐year‐old female with a solitary nodule on the chin whose case was referred to our institution for confirmation of the diagnosis of LCH. Skin biopsy showed an ulcerated nodule containing a wedge‐shaped infiltrate comprised of large atypical cells and cells with prominent grooved nuclei. The constellation of histologic and immunologic features favored a CD30 lymphoproliferative disorder of T‐cell lineage even though there were accompanying numerous dendritic histiocytes and CD1a positive Langerhans cells. The sheets of CD30 positive atypical lymphoid cells which express T‐cell markers were consistent with CD30 positive lymphoproliferative disease and favor CD30 positive anaplastic large‐cell lymphoma (ALCL) over Langerhans histiocytosis. The absence of Anaplastic Lymphoma Kinase (ALK) staining favored a primary cutaneous origin. This case signifies a CD 30+ ALCL of the skin which histopathologically mimics a LCH. Ezra N, Van Dyke GS, Binder SW. CD30 positive anaplastic large‐cell lymphoma (ALCL) mimicking Langerhans cell histiocytosis (LCH).     

Sézary's syndrome. Case report]

A patient with Sézary syndrome is presented. The symptoms persisted for 5 years when a sudden involvement of internal organs led to the death of the patient. Much evidence indicates that the Sézary syndrome is a special form of mycosis fungoides with erythroderma and a constant release of atypical cells into the blood. The nature of the Sézary cell has not yet been clearly elucidated. Cytogenetic and immunological findings identified the Sézary cell as an abnormal T-lymphocyte whereas cytochemical data support the concept of the presence of different atypical cell populations with lymphocytic respectively monocytic character.     

Dual surface makers and HTLV-I proviral DNA in a cutaneous tumour nodule in a case of adult T cell leukaemia/lymphoma

The phenotypic and morphological profiles of atypical cells in a case of adult T cell leukaemia/lymphoma were studied using a panel of monoclonal antibodies and electron microscopy. Retroviral sequence restriction analysis showed the presence of human T cell leukaemia/lymphoma virus type I (HTLV-I) in the skin lesion. Our case showed several unique features in the clinical, haematological, histopathological and immunohistochemical findings. An erythematous plaque and tumour nodules in the skin were found without any abnormal lymphocytes such as flower cells in the peripheral blood and bone marrow HTLV-I proviral DNA was detected in the skin tumour cells but not in the peripheral blood lymphocytes, and in the tumour nodule, atypical cells showed a distinct difference in morphology between cerebriform cells in the upper dermis and large lymphoid cells in the lower dermis. The cerebriform cells had, immunohistochemically, a T helper/inducer (Th/i) phenotype whereas the large lymphoblastoid cells possessed both the Th/i and T suppressor/cytotoxic (Ts/c) phenotypes. Ki-I antigen was detected in the large lymphoblastoid cells, but not in the cerebriform cells.     

An Aggressive Spindle Cell Squamous Carcinoma Arising in a Patient with Long-standing Erythroderma

Spindle cell squamous carcinoma (SCSC) of the left hand arising in a patient with longstanding erythroderma is reported. Histopathologically, spindle shaped atypical cells were observed neighboring the cells of well differentiated squamous cell carcinoma. These two types of tumor cells, spindle cells and well differentiated cells, were present side by side and merged into each other. The erythroderma had been present for over 20 years, and both clinical and histopathological findings suggested cutaneous T cell lymphoma, but were not diagnostic for mycosis fungoides, Sézary syndrome, or adult T cell lymphoma. Flow cytometry of peripheral blood cells showed a low CD4/CD8 ratio which suggested impaired T cell function. Multiple metastases of SCSC occurred in a short period and the patient died ten months after his first visit to us. The aggressive course of this case was unusual, and may be due to immunological abnormalities associated with the long standing erythroderma with impaired T cell function.     

Detection of HTLV-I proviral DNA in sarcoidosis

'Sarcoidosis-lymphoma syndrome' is known as an association of sarcoidosis with malignant lymphoma. We report a 56-year-old woman with systemic sarcoidosis who was seropositive for antibody against human T cell lymphoma/leukemia virus type I (HTLV-I). This patient showed integration of HTLV-I proviral DNA within cutaneous sarcoid nodules, but not in peripheral blood mononuclear cells. Neither atypical lymphocytes nor a T cell receptor beta1 gene rearrangement were observed in peripheral blood mononuclear cells or in cutaneous nodules, indicating that the patient did not have a smouldering type of adult T cell lymphoma/leukemia. Detection of integration of HTLV-I proviral DNA in cutaneous sarcoid nodules could suggest that the sarcoid nodules might have been generated as a protective response to chronic stimuli of HTLV-I.     

Adult T‐cell leukemia–lymphoma associated with follicular mucinosis

Follicular mucinosis (alopecia mucinosa) is often associated with malignancies including mycosis fungoides and Sézary syndrome, but not adult T‐cell leukemia–lymphoma (ATLL). We report a 49‐year‐old male patient who had pruritic follicular papules and erythemas clinically, and follicular and perifollicular infiltrates and follicular mucin deposition histopathologically. The patient showed 11% of flower‐shaped atypical lymphocytes in blood examination and positive human T‐cell leukemia virus type 1 antibody in serology, consistent with the chronic type of ATLL. This case seems to be a very rare association of follicular mucinosis and chronic ATLL, suggesting that malignant T cells may have a feature of folliculotropism as well as epidermotropism.     

Adult T cell leukemia accompanied by annular elastolytic giant cell granuloma

We report a 74-year-old Japanese patient with adult T-cell leukemia who concurrently developed annular elastolytic giant cell granuloma. Initially, itchy granulomatous lesions developed on his face, nape of the neck and dorsa of the hands, but gradually erythematous plaques appeared on the back and lower limbs. The histology of the granulomatous lesions revealed coexistence of an epithelioid cell granuloma with giant cells that phagocytosed elastic fibres in the dermis and Pautrier's microabscesses in the overlying epidermis. Subsequent sequential histological studies of an erythematous plaque revealed the development of granulomatous changes in pre-existing lymphomatous lesions. Laboratory data revealed the presence of antibody to human T cell leukemia/lymphoma virus I and 14,200 white cells/mm3 in the peripheral blood with 2% atypical lymphocytes which eventually amounted to 30%, one month before his death.     

Lymphoma- and leukemia-associated cutaneous atypical CD30+ T-cell reactions

Cutaneous CD30+ lymphoid infiltrates appear cytologically atypical and occasionally may be misinterpreted as recurrent disease when they occur in patients treated for other primary hematologic malignancies. We recently encountered two such cases and present our findings. One patient with B-cell lymphoma and another with myeloid leukemia developed cutaneous eruptions after chemotherapy displaying highly atypical perivascular lymphoid cells on histology that mimicked recurrent disease. In both cases, the lymphocytes were CD30+ T cells by immunohistochemistry. The skin lesions spontaneously resolved and have not recurred. Because one case was initially misinterpreted as recurrent leukemia, we conclude that close clinical correlation and immunophenotypic confirmation should be done for atypical cutaneous lymphoid infiltrates in patients with primary hematologic malignancies. We discuss the differential diagnosis of atypical CD30+ infiltrates in this setting, which include recurrent lymphoma or myeloid leukemia, primary cutaneous anaplastic large cell lymphoma (ALCL), lymphomatoid papulosis (LyP), carbamazepine-induced CD30+ pseudolymphoma, viral infection and an atypical eruption of lymphocyte recovery.     

Lymphomatoid papulosis expresses immunophenotypes associated with T cell lymphoma but not inflammation

Twelve skin biopsy specimens of lymphomatoid papulosis from nine patients were studied immunohistologically. The large atypical cells morphologically resembled Reed-Sternberg cells in six cases and large cerebriform mononuclear cells in three cases. These cells expressed pan-T cell antigens (Leu-4 and/or Leu-5) and helper T cell antigen (Leu-3) in each case. They also expressed activation antigens: HLA (human lymphocyte antigen)-DR, HLA-DQ, Tac, and T9. Reactivity of many nuclei with Ki-67 indicated a high proliferative index. Phenotypic abnormality of the large atypical cells was evident by their deficiency of T cell antigens Leu-1 and/or Leu-9 in eight of nine cases. Neither Ki-1 nor Leu-M1 were reliable markers for lymphomatoid papulosis in this series, since large atypical cells were Ki-1-positive in only three of eight cases and were Leu-M1-negative in all eight cases tested. The remainder of the cutaneous infiltrate consisted of small T cells, macrophages, Langerhans cells, and granulocytes. The small T cells expressed a normal phenotype except in some cases associated with mycosis fungoides in which they were deficient in various T cell antigens. Comparison of concurrent lymphomatoid papulosis and mycosis fungoides skin biopsy specimens in two patients revealed that they were composed of phenotypically distinct T cell subpopulations. These results indicate that the large atypical cells of lymphomatoid papulosis are a proliferating population of activated helper T cells that are deficient in certain T cell antigens. Such abnormal T cell phenotypes are common in T cell lymphoma but are rarely, if ever, observed in cutaneous inflammation. In conjunction with the cytologic atypia, aneuploidy, and association with other lymphomas documented in this or previous reports, these data suggest that lymphomatoid papulosis represents a T cell lymphoproliferative disorder rather than an inflammatory disorder.     

非霍奇金淋巴瘤1例

报告1例以皮肤肿瘤为首发表现的儿童非霍奇金淋巴瘤。患儿女,8岁。右侧鼻翼出现肿块3个月余,伴进行性增大1个月就诊。体格检查示局部淋巴结不增大,系统检查无异常。皮损组织病理检查示真皮内有异形淋巴样细胞浸润,免疫组化染色结果示：CD45RO（＋）,CD20,HMB45,CK,CD30和CD68均阴性,证实为T细胞淋巴瘤。     

Xanthomatized atypical T cells in a patient with mycosis fungoides and hyperlipidemia.

BACKGROUND--Lipoprotein-T-cell interactions are being reported with increasing frequency, and there is evidence that lipoproteins play a role in immunoregulation. We describe a patient with mycosis fungoides and hyperlipidemia who developed xanthomatization in one preexisting plaque. The case is unique in that some of the lipidized cells were atypical T cells. In previously reported cases of mycosis fungoides with dystrophic xanthomatosis, the lipid-containing cells have been identified only as histiocytes. OBSERVATIONS--Immunopathologic features, electron microscopy, and lipid stains of the xanthomatized plaque demonstrated that some of the lipid-laden cells were atypical T cells. CONCLUSIONS--In mycosis fungoides, malignant T cells may be intimately involved in processing of tissue lipids. We suggest that low-density lipoprotein receptors on activated T cells facilitated the cytoplasmic lipidization in this case.     

T cell receptor-gamma gene analysis of CD30+ large atypical individual cells in CD30+ large primary cutaneous T cell lymphomas

The hallmark of primary cutaneous CD30+ large T cell lymphoma are large lymphoid tumor cells, at least 75% of which, by definition, must be positive for CD30. The relatively benign clinical course of this lymphoma type has been explained with CD30-induced apoptosis, on the assumption that expression of CD30 defines the tumor clone; however, this hypothesis has not been tested on the molecular level to date. In this study we analyzed CD30+ cells in four patients with primary cutaneous CD30+ large T cell lymphoma by single cell polymerase chain reaction of T cell receptor-gamma genes followed by sequencing. Here, we demonstrate that most of the large CD30+ atypical cells possessed identical T cell receptor-gamma gene rearrangements, indicative of clonal proliferation. Nevertheless, polyclonally rearranged T cells were present in all CD30+ samples studied. In addition, one patient showed a second clone in a separate biopsy and three of four patients showed chromosomal imbalances as revealed by comparative genomic hybridization. Taken together, our data suggest that the CD30+ population in primary cutaneous CD30+ large T cell lymphoma indeed contains the tumor clone, thus providing molecular support for a link between clinical course and CD30-related signaling. Importantly, however, CD30 expression does not define the tumor clone as bystander T cells, as well as occasional additional clones, are also present in this population.     

Atypical cells in lymphomatoid papulosis express the Hodgkin cell-associated antigen Ki-1

Lymphomatoid papulosis (LyP) is characterized by the presence of large multinucleated cells resembling Reed-Sternberg (RS) cells. Evidence of antigenic similarity between these two cell types has been sought by immunohistologic labeling of 10 biopsies from cases of LyP with monoclonal antibodies against Ki-1 and other RS and Hodgkin (H) cell-associated antigens. In all cases studied, a proportion of the large atypical cells expressed the Ki-1 antigen. On the contrary, in 20 biopsies of benign skin lesions or cutaneous T-cell lymphomas, Ki-1-positive cells were absent or only occasionally present. Furthermore the large atypical cells of LyP also expressed antigens (e.g., T3, T4, HLA-DR, IL-2 receptors) which we have previously demonstrated on RS cells in the majority of cases of Hodgkin's disease (HD). These findings, in conjunction with the observation that Ki-1 antigen expression can be induced on peripheral blood lymphocytes following exposure to phytohemagglutinin or HTLV I, provide evidence that the Ki-1 positive cells in LyP represent activated T cells as RS cells do in many cases of HD.     

Primary effusion lymphoma presenting as a cutaneous intravascular lymphoma

Primary effusion lymphoma (PEL) is a rare and aggressive lymphoma that arises in the context of immunosuppression and is characterized by co‐infection with Epstein–Barr virus (EBV) and human herpesvirus‐8/Kaposi sarcoma‐associated herpesvirus (HHV‐8/KSHV). It was originally described as arising in body cavity effusions, but presentation as a mass lesion (extracavitary PEL) is now recognized. Here, we describe a case of PEL with an initial presentation as an intravascular lymphoma with associated skin lesions. The patient was a 53‐year‐old man with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) who presented with fevers, weight loss and skin lesions concerning for Kaposi sarcoma (KS). A skin biopsy revealed no evidence of KS; however, dermal vessels contained large atypical cells that expressed CD31 and plasma cell markers but lacked most B‐ and T‐cell antigens. The atypical cells expressed EBV and HHV‐8. The patient subsequently developed a malignant pleural effusion containing the same neoplastic cell population. The findings in this case highlight the potential for unusual intravascular presentations of PEL in the skin as well as the importance of pursuing microscopic diagnosis of skin lesions in immunosuppressed patients.     

Cutaneous extranodal NK/T‐cell lymphoma mimicking cellulitis an HIV positive patient without lymphopenia

We present the case of a 28‐year‐old male with a history of human immunodeficiency virus (HIV) with a 1‐month history of a steadily enlarging, firm painful lesion on the right posterior shoulder. The patient was initially treated for cellulitis given his clinical picture. Histopathologic examination revealed an angiocentric and dermal proliferation of markedly atypical lymphoid cells with numerous mitoses and apoptotic bodies along with broad zones of necrosis. Biopsy revealed the presentation to be consistent with NK/T‐cell lymphoma. The cutaneous lesions from NK/T‐cell lymphoma can often be initially mistaken for cellulitis, therefore this malignancy should be included on the differential in a patient HIV/acquired immune deficiency syndrome (AIDS).     

Loss of CD30 expression after treatment with brentuximab vedotin in a patient with anaplastic large cell lymphoma: a novel finding

Anaplastic large cell lymphoma (ALCL) is an aggressive T‐cell lymphoma characterized by strong and uniform expression of CD30. Brentuximab vedotin (BV), an anti‐CD30 antibody‐drug conjugate has been approved by the U.S. FDA for relapsed/refractory systemic ALCL and achieves improved outcomes. We report a 44‐year‐old African‐American man who presented with lymphadenopathy, lip and chest nodules diagnosed as CD30+, ALK‐negative ALCL. The patient was treated with BV upon recurrence. While on treatment, the patient developed new‐onset nodules on the chest and back. Skin biopsy showed a diffuse dermal infiltrate of medium‐to‐large atypical lymphocytes with frequent mitosis and scattered eosinophils. Immunohistochemically, the atypical cells displayed the same immunophenotype as previous specimens (CD3+, CD4?/CD8?, CD56?, ALK? and TCR γ?), except for lack of CD30 expression which was attributed to BV treatment effect. The diagnosis was thought to be consistent with ALK‐negative ALCL and the patient was continued on BV along with total skin electron beam radiation and the lesions cleared. The patient relapsed 2 months later with extensive disease and expired. In summary, this is the first report in the literature of loss of CD30 expression in ALCL after BV therapy. Awareness of this may prevent a mistaken diagnosis of a CD30‐negative secondary T‐cell lymphoma.     

Photodynamic therapy efficiently controls dermatophytosis caused by Trichophyton rubrum in a murine model

Hydroa vacciniforme (HV) is a rare photodermatosis that mainly affects children and manifests as vesiculopapular eruptions in sun‐exposed areas without systemic symptoms. HV‐like lymphoma (HVLL) is one of the Epstein–Barr virus (EBV)‐associated lymphoproliferative disorders (LPD) of childhood. Its diagnosis is based on monoclonal T‐cell proliferation; however, its degree of malignancy is controversial owing to its variable prognosis. Elderly‐onset cases of these diseases are extremely rare, and the clinical features remain unknown. It has been shown that late onset is closely associated with a severe phenotype in EBV‐associated LPD including atypical HV. Here we describe a case of elderly‐onset atypical HV accompanied by T‐cell monoclonality, but with a very indolent clinical course. Our patient indicates a possible case with elderly‐onset atypical HV manifesting a favourable course, and that T‐cell monoclonality and age of onset cannot always predict the disease severity, and highlights the difficulty of prognosis prediction in elderly‐onset atypical HV.