The expression of the Hodgkin's disease-associated antigen Ki-1 in cutaneous infiltrates

Reactivity for Ki-1 antibody was studied in 145 patients with a large variety of cutaneous disorders. The antigen was consistently expressed and by a high proportion of tumour cells in infiltrates in which atypical cells revealed a 'histiocytic' appearance, i.e. lymphomatoid papulosis (LP), T-immunoblastic lymphoma with the characteristic of true histiocytic lymphoma, Hodgkin's disease, T-blast cell proliferation with giant multivesicular bodies, concurrent LP and mycosis fungoides (MF), and two cases of MF. Ki-1+ cells with the usual morphology of atypical T-cells formed a major component in 2 other cases of MF, and a minor component in 7 other cases of MF. A possible non-neoplastic counterpart was found in small to medium-sized Ki-1+ cells, including blast cells, which occurred occasionally in the T-cell infiltrates of eczema, actinic reticuloid, lichen planus and pityriasis lichenoides. Small Ki-1+ cells which were observed in the reactive B/T cell component of lymphocytoma cutis but also in similar components occurring occasionally in non-epidermotropic cutaneous T-cell lymphoma, and malignant B-cell lymphomas, might be analogous to the Ki-1+ cells in normal lymphoid tissue.     

Primary cutaneous pleomorphic T-cell lymphoma expressing CD30 antigen.

Pleomorphic peripheral T-cell lymphomas (PPTL) arising primarily in the skin are uncommon. The observation of pleomorphic T-cell lymphoma composed of 100% CD30+ cells is rare. We report the case of a woman in whom such a tumor manifested itself with a single cutaneous lesion. It was composed of medium to large cells expressing markers of helper/inducer T-lymphocytes, as well as activation (CD30) and proliferation antigens (Ki-67), but not the CD25 activation antigen. The lesion was excised and the patient is alive and disease free 2 years after the diagnosis. This case confirms previous reports about the favorable course of some cutaneous pleomorphic lymphomas, and shows that the activation antigen expression and proliferation antigen (Ki-67) expression do not seem to worsen the prognosis.     

Adult T-Cell Leukemia/Lymphoma and Cutaneous T-Cell Lymphoma Are They Related?

Comparative studies were performed on clinical and laboratory features of four patients with different types of T-cell lymphoma of the skin; adult T-cell leukemia/lymphoma (ATLL), Sézary syndrome, mycosis fungoides, and Ki-1-positive lymphoma. All neoplastic cells studied showed a helper-inducer T-cell phenotype. A Ki-1-positive lymphoma is distinct from other types of cutaneous lymphomas because of unique morphologic and phenotypic features. Clonal proliferation of lymphocytes infected by human T-cell lymphotrophic virus (HTLV)-1 distinguishes ATLL from other T-cell lymphomas of the skin, especially in the endemic area of ATLL. From the pathogenic point of view, ATLL should not be included in a group with mycosis fungoides and Sézary syndrome.     

Cutaneous histiocytic malignancy. Immunohistochemical re-examination of cases previously diagnosed as cutaneous "histiocytic lymphoma" and "malignant histiocytosis"

True histiocytic lymphoma (THL) and malignant histiocytosis (MH) have been defined by clinical and histologic findings and enzyme histochemistry. We reviewed cases previously diagnosed as cutaneous histiocytic lymphoma (HL) and MH with cutaneous lesions. These cases had been classified as "histiocytic" on the basis of previous enzyme histochemistry profiles of frozen tissue. Cutaneous tumor cells were reevaluated using a panel of immunohistochemical stains in formalin-fixed, paraffin-embedded tissue in correlation with histopathologic examination. The antibodies used in this study were directed against CD45 (leukocyte common antigen [LCA]), CD20 (L26) for B cells, CDS and CD45RO (UCHL-1) for T cells, CD68 (KP-1) and lysozyme for histiocytes, as well as CD30 (BerH2) for Ki-1 positive cells. On re-evaluation, the seven cases originally classified as HL were reclassified as one case of THL with neoplastic cells positive for CD68 (KP-1) and lysozyme, two cases with immunohistochemical features of Ki-1 lymphoma (including one of T-cell lineage), three cases of T-cell lymphoma, and one case of B-cell lymphoma, all associated with variable degrees of reactive histiocytosis. The four cases originally classified as MH were reclassified as two cases of MH and two cases of uncertain lineage. Although rare, histiocytic malignancies do exist. However, the diagnosis of histiocytic malignancy should be made only after careful correlation of atypical tumor cells in histopathologic sections and sections stained immunohistochemically. Erroneous classification of reactive histiocytes as neoplastic histiocytes using only enzyme histochemistry in frozen sections is a pitfall to be avoided.     

A Case of Ki-1 Positive Anaplastic Large Cell Lymphoma Transformed from Mycosis Fungoides

A case of cutaneous Ki-1 positive anaplastic large cell lymphoma which developed in the plaque stage of mycosis fungoides was described. A 73-year-old woman who had suffered from pruritic scaly eruptions over her entire body for more than two decades was admitted because of an ulcerated tumor measuring 45 times 55 times 15 mm and several satellite tumors on the buttock. All tumorous lesions were resected without recurrence to date. Histochemical study revealed that the tumor consisted of large anaplastic cells which were Ki-1 (CD30)-positive and LCA-negative. Some of the erythematous plaques contained LCA-positive, small-sized atypical lymphocytes. In other plaques which developed two years later, there were large Ki-1-positive atypical cells. In the specimens obtained from the tumor and the plaque, the same pattern of T-cell receptor gene rearrangements was detected. These findings indicate that both Ki-1 positive anaplastic cells in the tumor and atypical lymphoid cells in the plaques were derived from the same T cell clone.     

Primary Cutaneous Ki-1+ Anaplastic Large Cell Lymphoma: A Morphologic,Immunohistochemical and Genetic Study of an Indolent Case

A 59-year-old woman with a large nodular ulcerative lesion on her neck was presented. She had a 3 year history of recurrent cutaneous nodules which spontaneously regressed before regional lymphadenopathies appeared. She has followed an indolent clinical course for seven years after the first overt lymphadenopathies appeared. Histological findings were compatible with anaplastic large cell lymphoma (ALCL). The tumor cells strongly expressed Ki-1 (CD30), HLA-DR, IL-2 receptor (CD25) and leukocyte common antigen. These findings led to the diagnosis of primary cutaneous Ki-1⁺ ALCL. Although the majority of the tumor cells did not express T-cell related antigens, the detection of monoclonal TCR gene rearrangement clearly established the T-cell lineage nature.     

原发性皮肤外周T细胞淋巴瘤(非特殊类型)1例

患者男,60岁。全身结节、肿块十余年。左大腿结节组织病理示:真皮全层及皮下组织大量瘤细胞呈结节状密集分布,瘤细胞形态呈多形性,胞体大,核异型,可见较多多核巨细胞。免疫组化示:CD2,CD3和TIA-1均阳性,CD4,CD5及CD8均弱阳性,CD7,CD20,CD30,CD56,GrB及ALK均阴性,Ki-67显示高增殖指数(70%)。诊断:原发性皮肤外周T细胞淋巴瘤(非特殊类型)。     

Ki-1+ cutaneous lymphoma. Gene rearrangement analysis of tumor cells in tissue and short-term culture of a patient

Cutaneous malignant lymphomas developed in an 80-year-old man without any evidence of leukemic disseminations of lymphoma cells. Immunohistologic staining showed the expression of Leu-3a, Leu-4, Ki-1, Tac, and HLA-DR antigens on tumor cells in tissue and large lymphoid cells in long-term, interleukin 2-containing culture of tumor explants. DNA samples extracted from the skin tumors and cultured lymphoid cells showed a clonal rearrangement of T-cell receptor (TCR) gene C beta 1 with the molecular size of 9 kilobases. These findings suggested the T-cell origin of Ki-1+ cutaneous lymphoma cells and the occurrence of a clonal proliferation of tumor cells in culture.     

Gene expression profile in a case of primary cutaneous CD30-negative large T-cell lymphoma with a blastic phenotype

A 65-year-old Japanese woman presented with disseminated erythematous patches, plaques, and nodules on the trunk and limbs. Histological examination showed diffuse and dense infiltrates located in the dermis and subcutis, composed of large pleomorphic T lymphocytes. Immunohistochemically, neoplastic cells were positive for blastic T-cell markers, but negative for CD30 (Ki-1) antigen. Based on the clinicopathological findings, a diagnosis of primary cutaneous large T-cell lymphoma was made. Despite systemic chemotherapy, the patient died 7 months after diagnosis. Gene expression profiling using complementary DNA microarrays indicated significantly increased expression of an apoptosis-inhibitory protein and certain cyokines and cytokine receptors (e.g. MCP-1, MCP-2, IP-10, and IL-2R gamma) in the tumour-indurated skin. Comprehensive gene expression patterning in additional cases may provide useful information regarding the biological and clinical behaviour of aggressive cutaneous lymphomas such as CD30-negative large T-cell lymphoma.     

原发性皮肤CD4+多形性小/中T细胞淋巴瘤一例

报告1例原发性皮肤CD4+多形性小/中T细胞淋巴瘤.患者男,19岁.全身多发暗红色斑块和小结节2年.皮损组织病理检查示,真皮内血管及附属器周围有致密小到中等大,胞质空亮,核扭曲的淋巴样细胞浸润,可见核分裂像.未见亲表皮性,但有浸润毛囊现象.免疫组化检查显示,CD3阳性、CD4阳性、CD8阴性、CD30阴性和CD20阴性,Ki-67阳性率约为25%.诊断:原发性皮肤CD4+多形性小/中T细胞淋巴瘤.     

原发性皮肤CD4^＋多形性小/中T细胞淋巴瘤一例

报告1例原发性皮肤CD4^＋多形性小/中T细胞淋巴瘤.患者男,19岁.全身多发暗红色斑块和小结节2年.皮损组织病理检查示,真皮内血管及附属器周围有致密小到中等大,胞质空亮,核扭曲的淋巴样细胞浸润,可见核分裂像.未见亲表皮性,但有浸润毛囊现象.免疫组化检查显示,CD3阳性、CD4阳性、CD8阴性、CD30阴性和CD20阴性,Ki-67阳性率约为25%.诊断：原发性皮肤CD4＋多形性小/中T细胞淋巴瘤.     

原发性皮肤CD4+多形性小/中T细胞淋巴瘤一例

报告1例原发性皮肤CD4+多形性小/中T细胞淋巴瘤.患者男,19岁.全身多发暗红色斑块和小结节2年.皮损组织病理检查示,真皮内血管及附属器周围有致密小到中等大,胞质空亮,核扭曲的淋巴样细胞浸润,可见核分裂像.未见亲表皮性,但有浸润毛囊现象.免疫组化检查显示,CD3阳性、CD4阳性、CD8阴性、CD30阴性和CD20阴性,Ki-67阳性率约为25%.诊断:原发性皮肤CD4+多形性小/中T细胞淋巴瘤.     

原发性皮肤CD4+多形性小/中T细胞淋巴瘤一例

报告1例原发性皮肤CD4+多形性小/中T细胞淋巴瘤.患者男,19岁.全身多发暗红色斑块和小结节2年.皮损组织病理检查示,真皮内血管及附属器周围有致密小到中等大,胞质空亮,核扭曲的淋巴样细胞浸润,可见核分裂像.未见亲表皮性,但有浸润毛囊现象.免疫组化检查显示,CD3阳性、CD4阳性、CD8阴性、CD30阴性和CD20阴性,Ki-67阳性率约为25%.诊断:原发性皮肤CD4+多形性小/中T细胞淋巴瘤.     

Cutaneous T cell lymphoma with suppressor/cytotoxic (CD8) phenotype: identification of rapidly progressive and chronic subtypes

We identified nine patients with cutaneous T cell lymphoma in whom the neoplastic cells expressed the CD8 (T8) suppressor T cell phenotype instead of the more common CD4 (T4) helper T cell phenotype. Five had rapidly progressive disease characterized by distinctive papulonodular skin lesions (four patients), involvement of palms or soles (four patients) or oral cavity (two patients), and poor response to standard topical therapy (four patients). Histologic examination showed extensive epidermotropism often associated with pagetoid features. Immunoperoxidase studies revealed a novel aberrant T cell phenotype characterized by lack of expression of CD4 and CD2 (T11) but positive staining for CD3 (T3) and CD7 (3A1). In contrast, the neoplastic cells from four patients with clinically more chronic CD8+ cutaneous T cell lymphoma, although also commonly epidermotropic, had a different aberrant T cell phenotype similar to that often seen in CD4+ mycosis fungoides; that is, there was lack of expression of CD7 but a positive reaction to staining for CD2. In two cases the tumor cells acquired the CD7 antigen or lost the CD2 antigen with progression of the disease. Two cases were analyzed with Southern blotting and both showed rearranged DNA bands that confirmed the presence of clonal populations of T cells. Our findings suggest the following: (1) CD8+ cutaneous T cell lymphoma can be rapidly progressive or chronic. (2) These two types cannot be reliably distinguished by histologic features. (3) Rapid progression was associated with a CD2-, CD7+ phenotype whereas chronicity was associated with a CD2+, CD7- phenotype.     

Immunologic differentiation of the Sézary syndrome due to cutaneous T-cell lymphoma and chronic actinic dermatitis

Peripheral blood mononuclear cells from two well-defined groups of patients with the Sézary syndrome have been studied employing indirect immunofluorescent and indirect immunogold techniques in light and electron microscopy, using monoclonal antibodies against T-cell subpopulations. Four patients had chronic actinic dermatitis (CAD) of the actinic reticuloid variant, with erythroderma. Eight patients had cutaneous T-cell lymphoma. All patients showed the clinical features of the Sézary syndrome, including erythroderma, palmoplantar hyperkeratosis, and peripheral lymphadenopathy, and in all patients significant numbers (0.5-30.5 X 10(9) cells/liter) of circulating mononuclear cells were observed with Sézary cell morphology on light-microscopic examination of blood films. Major differences were observed in the circulating T-cell subpopulations in the two groups. In the erythrodermic CAD patients, there was a moderately elevated T-cell count (1.6 +/- 0.6 X 10(9) cells/liter; normal, 1.0 +/- 0.3 X 10(9) cells/liter) of which the majority of the cells was suppressor T cells (OKT8+) giving a very low helper:suppressor T-cell ratio of 0.1:1-0.36:1 (normal, 1.7:1-3.5:1). In cutaneous T-cell lymphoma, there was also an elevation of the T-cell count (9.5 +/- 12.9 X 10(9) cells/liter), but in these patients the predominant cell was the helper T cell (OKT4+) with a high helper:suppressor T-cell ratio of 3.7:1-98:1.     

Primary cutaneous CD30+ anaplastic large-cell lymphoma in a young patient with psoriasis

Psoriasis is a common chronic inflammatory cutaneous disease, while primary cutaneous CD30+ anaplastic large-cell lymphoma (PC-ALCL) is a rare T-cell lymphoma which always has an excellent prognosis, although multifocal PC-ALCL tends to relapse after systemic chemotherapy. Psoriasis associated with PC-ALCL is exceptionally rare. We report a 29-year-old Chinese female with a 5-year history of psoriasis treated with Chinese herbs alone, who was referred to our institution with a tumor on the left clavicular region for 1 year and another one on the left palm for 2 months. Skin biopsies of both lesions showed diffuse infiltration of tumor cells, composed of large atypical cells with marked nuclear pleomorphism, prominent nucleoli, and eosinophilic cytoplasm. Large numbers of neutrophilic infiltrations were also noted in the lesion. Immunostaining revealed the lesion to be positive for CD30, vimentin, CD45, and CD68, and weakly positive for epithelial membrane antigen, but negative for anaplastic lymphoma receptor tyrosine kinase. The patient was diagnosed to have psoriasis associated with PC-ALCL; she died 18 months after the final diagnosis with unknown cause. We consider that immune dysregulation and/or Chinese herbs may play roles in the development of the present PC-ALCL.     

Adult T-cell leukemia/lymphoma: a retroviral malady

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive leukemia/lymphoma of mature T-lymphocytes caused by human T-cell lymphotropic virus type 1 (HTLV-1). At a tertiary healthcare center in South India, a 58-year-old female presented with multiple erythematous, crusted, and umbilicated papules over the body along with cervical lymphadenopathy. The skin biopsy was consistent with cutaneous T-cell lymphoma. Although she responded initially to chemotherapy, the disease relapsed after 3 months, and she developed disseminated infiltrated skin lesions, generalized lymphadenopathy, and leukemia. Due to the unusual clinical findings we did HTLV-1 Enzyme-linked immunosorbent assay (ELISA), which turned out to be positive in high titers. Her mother had died at an early age from a hematological malignancy and her daughter was also found to be seropositive. To the best of our knowledge, this is the first case to be reported from India of the chronic type of ATLL associated with mother-to-child transmission of HTLV-1 in two generations. This case also emphasizes that the chronic type of ATLL can occur in nonendemic areas like India and should be suspected in nonresponding cases of mycosis fungoides. It should be kept in mind that the chronic type often presents without hypercalcemia or the characteristic 'flower cells' in the peripheral smear.     

Monoclonal T-cell dyscrasia of undetermined significance associated with recalcitrant erythroderma

BACKGROUND: Erythroderma is a diffuse, inflammatory skin reaction that, in rare instances, is associated with hematologic malignancies such as cutaneous T-cell lymphoma (erythrodermic mycosis fungoides) or T-cell leukemia (Sezary syndrome or adult T-cell leukemia/lymphoma). OBSERVATIONS: We screened 30 patients with erythroderma (20 patients with erythroderma of known etiology and 10 patients with idiopathic erythroderma) for the presence of circulating monoclonal T-lymphocyte populations using T-cell receptor (TCR)-gamma gene-specific polymerase chain reaction and automated capillary DNA electrophoresis. Moreover, the phenotypic analysis of peripheral blood CD4+ lymphocytes was performed using the following surface markers: CD3, CD7, CD8, CD25, CD26, CD27, CD28, CD29, CD30, CD45RO, CD45RA, CD56, CD134, HLA-DR, TCRalphabeta, TCRgammadelta, and cutaneous lymphocyte antigen (CLA). In 5 patients with idiopathic erythroderma we detected T-cell clones in peripheral blood (in 1 case, associated with the presence of the same clone in the skin) and a 2-fold increase in the proportion of CD3+ CD4+ CD7- CD26- cells. Cell depletion studies indicated that the monoclonal T cells were present within the CD4+ CD7- cell population. Clinically, all patients had chronic, recalcitrant erythroderma but none developed any hematological malignancy during their lifetimes or fulfilled the criteria for cutaneous lymphoma or Sezary syndrome. CONCLUSIONS: A proportion of patients with chronic erythroderma present with the monoclonal expansion of CD4+ CD7- CD26- lymphocytes in their blood. This condition represents a probably benign T-cell dyscrasia, or one of very low malignancy. Alongside monoclonal gammapathy of undetermined significance (MGUS) and monoclonal (B-cell) lymphocytosis of undetermined significance (MLUS), we propose using monoclonal T-cell dyscrasia of undetermined significance (MTUS) to underline a conceptual similarity between this disorder and the more common types of lymphocytic dyscrasia.     

Cutaneous T-cell lymphoma: utility of antibodies to the variable regions of the human T-cell antigen receptor.

BACKGROUND: The clonotypic 90 kd Ti heterodimer of the human T-cell antigen receptor is composed of two distinct chains (alpha beta or rarely tau delta) that result from the recombination of variable (V), constant, joining, and, in the case of beta chains, additional diversity regions. OBJECTIVE: The variable region expression of human cutaneous T-cell lymphoma (CTCL) was studied. METHODS: Biopsy specimens from 13 patients with CTCL (7 plaque, 3 tumor stage, 3 Sézary syndrome) were examined immunohistochemically by a panel of seven commercially available monoclonal V-region antibodies. RESULTS: Two patients had significant anti-V-region staining. One patient with Sézary syndrome had two lesions, subjected to biopsy 4 months apart, that reacted with beta V5(a), a specificity previously documented by flow cytometry of leukemic cells. A patient with plaque-stage CTCL, negative for T-cell gene rearrangement by Southern blot, demonstrated reactivity with beta V5(c) largely limited to epidermotropic lymphocytes. CONCLUSION: Panels of V-region antibodies should be useful reagents for diagnosis and follow-up of CTCL.     

种痘样水疱病样T细胞淋巴瘤伴发原发性皮肤CD30阳性大细胞淋巴瘤1例

患者女,17岁。全身反复起丘疹、水疱、坏死、凹陷状瘢痕伴瘙痒、发热15年,四肢起肿块2年。血清抗EBV-IgM(-),抗EBV-IgG(+)。肿块处皮损组织病理示真皮中下层和皮下组织见弥漫性致密的瘤细胞浸润,细胞核呈间变性;免疫组化示CD3(+),浸润的大细胞CD30(+),CD43(+),80%浸润细胞Ki-67(+)。水疱处皮损组织病理示表皮网状变性及多个水疱,真皮和皮下组织可见血管和附属器周围以淋巴细胞为主的、伴少量嗜酸粒细胞浸润,部分浸润细胞呈明显异形性;免疫组化示CD3(+),CD30(-),CD43(+),Ki-67(+)。诊断:种痘样水疱病样T细胞淋巴瘤伴发原发性皮肤CD30阳性大细胞淋巴瘤。确诊后建议患者转肿瘤科化疗,随访中。