Immunohistochemical studies using monoclonal antibodies on lymph nodes from patients with mycosis fungoides and Sézary''s syndrome

Using an indirect immunoperoxidase technique and a panel of monoclonal antibodies with well-defined specificities, the authors studied the distribution of lymphoid and nonlymphoid cells in the T-cell areas of both involved and uninvolved lymph nodes from patients with mycosis fungoides (MF) and Sézary's syndrome (SS) and dermatopathic lymph nodes from patients with generalized benign skin disease. The distribution of the different T-cell subsets, HLA-DR+ interdigitating cells and OKT6+ Langerhans cells, in the paracortical areas of MF lymph nodes showing features of dermatopathic lymphadenopathy with early involvement, as assessed after conventional histologic examination, was similar to that of dermatopathic MF lymph nodes without early involvement and lymph nodes from patients with generalized benign skin disease, indicating that these studies do not provide additional criteria for the early diagnosis of MF involvement. MF lymph nodes showing partial or complete obliteration of the normal architecture tended to have lower numbers of HLA-DR+ interdigitating cells and OKT6+ Langerhans cells, but showed increased numbers of blast cells, part of which had lost their mature helper-T-cell phenotype. These differences between the early and advanced stages of lymph node involvement by MF were analogous to those observed in the different stages of cutaneous involvement, as described previously. The lymph nodes from patients with SS were diffusely infiltrated by neoplastic T cells that had retained their mature helper-T-cell phenotype (Leu-1+, 3a+, 4+), contained very low numbers of Leu-2+ T-cells and relatively few HLA-DR+ interdigitating cells and OKT6+ Langerhans cells. These different staining patterns in MF and SS lymph nodes may reflect different pathogenetic mechanisms.     

Immunophenotypic characterization of the cutaneous exanthem of SIV-infected rhesus monkeys. Apposition of degenerative Langerhans cells and cytotoxic lymphocytes during the development of acquired immunodeficiency syndrome.

A T-cell tropic retrovirus, simian immunodeficiency virus (SIV), has recently been isolated from immunodeficient rhesus monkeys. This virus has remarkable similarities to human immunodeficiency virus (HIV), the etiologic agent of acquired immunodeficiency syndrome. Subsequent studies of simian infection with SIV have shown it to be a relevant animal model for studying the pathogenesis of AIDS in man. In both HIV-infected humans and SIV-infected monkeys, a cutaneous maculopapular eruption has been described. To date, the pathogenesis and possible relationship of these exanthema to the evolution of systemic immunosuppression have remained obscure. In this study, the mononuclear cell infiltrates that characterize skin rashes of SIV-infected rhesus monkeys were found to be composed predominantly of cells with phenotypic characteristics of cytotoxic/suppressor (T8+) lymphocytes and natural killer cells. Many of these cells expressed membrane-bound interleukin-2 receptor molecules. Double labeling and immunoelectron microscopy revealed these cells in direct contact with degenerative Langerhans cells within the epidermis and dermis. These observations suggest that the cutaneous rash associated with SIV infection may be the consequence of target cell injury of Langerhans cells by effector cells with cytotoxic potential.     

Immunohistochemical study of epidermal Langerhans cells and dermal dendritic cells in benign and malignant skin lesions characterized by a dermal lymphoid infiltrate consisting either of B-cells or T-cells

Summary Skin biopsies from 43 patients with a rather dense dermal lymphoid infiltrate of either inflammatory or neoplastic nature have been investigated. We studied the number, distribution and immunophenotype of epidermal Langerhans cells and dermal dendritic cells. As previously reported, differences in epidermal Langerhans cell and dermal dendritic cell numbers between skin biopsies with a B-cell infiltrate and skin biopsies with a T-cell infiltrate were found, dendritic cells being more numerous in the latter. The main finding of this study was an uneven distribution of epidermal Langerhans cells and dermal dendritic cells in skin biopsies with a T-cell infiltrate: in skin lesions with an inflammatory lymphoid infiltrate, small clusters of epidermal and dermal dendritic cells admixed with T-lymphocytes (predominantly T-helper/inducer cells) and small blood vessels were present at areas of exocytosis. In skin lesions with a neoplastic lymphoid infiltrate larger, more loosely arranged aggregates of dendritic cells and T-cells were seen. These cell aggregations composed of activated (inflammatory or neoplastic) T-cells and dendritic cells may represent the cutaneous homologue of the secondary T-nodule in the lymph node. Both types of cell aggregates may correspond to the dendritic cell-T cell clusters observed in in vitro induced immune responses.Presented at the XVIth International Congress of the International Academy of Pathology and 7th World Congress of Academic and Environmental Pathology in Vienna, 1986Aspirant of the NFWO (Nationaal Fonds voor Wetenschappelijk Onderzoek)     

Radioimmunodetection of cutaneous T-cell lymphoma with 111In-labeled T101 monoclonal antibody

T101 monoclonal antibody recognizes a pan-T-cell antigen present on normal T cells and also found in high concentrations in cutaneous T-cell lymphoma. We used this antibody, radiolabeled with 111In, in gamma-camera imaging to detect sites of metastatic cutaneous T-cell lymphoma in 11 patients with advanced disease. In all patients, [111In]T101 concentrated in pathologically or clinically detected nodes, including those in several previously unsuspected nodal regions. Concentrations (per gram of tissue) ranged from 0.01 to 0.03 percent of the injected dose and were consistently 10 to 100 times higher than previously reported on radioimmunodetection. Focal uptake was seen in skin tumors and heavily infiltrated erythroderma but not in skin plaques. The specificity of tumor targeting was documented by control studies with [111In]chloride or [111In]9.2.27 (anti-melanoma) monoclonal antibody. Increasing the T101 dose (1 to 50 mg) altered distribution in nontumor tissues. These studies suggest that imaging with [111In]T101 may be of value in identifying sites of cutaneous T-cell lymphoma. In contrast to the targeting of solid tumors, the mechanism of localization appears to be related to binding to T cells, which can then carry the radioactivity to involved sites.     

Clonal composition of T cells in lymphomatoid papulosis.

A cDNA of the C beta 2 gene of the T-cell receptor was used as a probe to investigate the clonal composition of T cells in skin lesions of 5 patients with lymphomatoid papulosis (LyP), a chronic recurrent eruption characterized by morphologically abnormal activated T cells in the cutaneous infiltrate. Clonal T-cell populations, as evidenced by rearranged DNA bands, were demonstrated in the skin lesions of four patients, one of whom has shown clinical progression toward lymphoma. Three of these patients had lesions of type A histology, a type previously shown to be associated with aneuploidy. The remaining patient with clonal lesions appeared to have the same gene rearrangement pattern in DNA obtained from separate lesions taken 11 months apart, providing evidence that the T cells in both sites were derived from the same clone. This patient had lesions of type B histology, which is not associated with aneuploidy. Absence of a rearranged band and deletion or near absence of the 10.8 kb band in Eco RI digests was interpreted as evidence of polyclonal T-cell hyperplasia, accounting for the skin infiltrate of a fifth patient who had a prolonged clinical course without progression to lymphoma. This patient had lesions of type A histology with frequent Ki-1-positive Reed-Sternberg-like cells. Our results show that gene rearrangement analysis provides information that is independent of histology in LyP and may in part explain the variable progression of LyP to lymphoma in 10-20% of patients.     

Composite mycosis fungoides and B-cell chronic lymphocytic leukemia

Concordant or composite mycosis fungoides and B-cell chronic lymphocytic leukemia (B-CLL) is exceedingly rare, with only 10 cases previously described to our knowledge. We report a case of a 64-year-old woman who developed generalized erythroderma 5 years after the diagnosis of early stage B-CLL. Over the next 6 years of her clinical course multiple sequential samples of skin, peripheral blood, and one enlarged lymph node were studied in detail by flow cytometry, immunohistochemistry, molecular diagnostics, and electron microscopy. The progressive cutaneous infiltrates were initially characterized as leukemia cutis, infiltration by B-CLL. Three years later, when she developed worsening skin disease and lymphadenopathy, the cutaneous infiltrates were characterized as cutaneous T-cell lymphoma. At that point, a biopsy of an enlarged lymph node revealed a composite lymphoma of both B-CLL and cutaneous T-cell lymphoma, and the peripheral blood also contained circulating cells of both neoplasms. Herein we summarize the literature on concordant cutaneous T-cell lymphoma and B-CLL, and the literature on concordant T- and B-cell neoplasms in general, with a review of the postulated relationships between these neoplasms.     

Analysis of clonality of atypical cutaneous lymphoid infiltrates associated with drug therapy by PCR/DGGE

Atypical lymphocytic infiltrates that mimic cutaneous lymphoma (ie, pseudolymphoma) are often observed in skin biopsy specimens from patients with altered immune function. The latter may reflect systemic immune dysregulatory states such as collagen vascular disease or human immunodeficiency virus infection. Among the iatrogenic causes are drug therapy with agents that abrogate lymphocyte function. These drugs encompass the anticonvulsants, antidepressants, phenothiazines, calcium channel blockers, and angiotensin-converting enzyme inhibitors. The appellation of lymphomatoid hypersensitivity reaction has been applied to cases of drug-associated pseudolymphoma. Pathologically and clinically, the distinction of such cases from cutaneous lymphoma is difficult. We employed the polymerase chain reaction (PCR) on archival material of proven drug-associated lymphomatoid hypersensitivity reactions both to explore its utility as an adjunct in diagnosis and to investigate the genotypic aberrations induced by drug therapy. Formalin-fixed, paraffin-embedded biopsy specimens from seven cutaneous T-cell lymphomas (CTCL), one nodal T-cell lymphoma, two cutaneous B-cell lymphomas, three typical hypersensitivity reactions, one tonsil, and 14 lymphomatoid hypersensitivity reactions were studied. Control cases for which DNA derived from fresh tissue was used include the Jurkat T-cell tumor line, placenta, one nodal B-cell lymphoma, and one case of reactive lymph node hyperplasia. DNA was obtained and purified by standard methods, then amplified with oligonucleotide primers specific for the T-cell receptor gamma locus and the immunoglobulin heavy chain genes. T-cell amplicons were analyzed by denaturing gradient gel electrophoresis (DGGE) and B-cell amplicons by either nondenaturing polyacrylamide or agarose gel electrophoresis. The nodal and Jurkat T-cell lymphomas, six of seven CTCL, one cutaneous B-cell lymphoma, and 2 of 14 lymphomatoid hypersensitivity reactions showed dominant ("monoclonal") T-cell gene rearrangement patterns, and the remainder of cases were polyclonal. A causal relationship between drug therapy and skin eruption was ascertained in the two patients showing T-cell rearrangements, and both experienced complete and sustained lesional resolution on discontinuation of the implicated drug. The only immunoglobulin heavy chain gene rearrangements detected by PCR were in two of the three B-cell lymphomas. We conclude that PCR/DGGE is a powerful method for assaying T-cell clonality in archival tissue and can aid in the discrimination of reactive from malignant cutaneous infiltrates with appropriate clinicopathologic correlation. Recognition that a monoclonal TCRgamma rearrangement can be observed in cases of drug-associated lymphomatoid hypersensitivity may help in avoiding a misdiagnosis of malignant lymphoma.     

Defective regulation of Epstein-Barr virus infection in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related disorders

Patients with the acquired immunodeficiency syndrome (AIDS) acquire undifferentiated B-cell lymphomas that are similar to African Burkitt's lymphoma and contain Epstein-Barr virus (EBV). Using an in vitro assay system that measures a complex of cellular responses to EBV-infected lymphocytes, we found that B cells from 7 patients with AIDS and from 10 patients with AIDS-related disorders produced abnormally low numbers of immunoglobulin-secreting cells (P less than 0.001 as compared with normal controls) and that T-cell suppression, which was greater than 80 percent in EBV-seropositive normal controls, was absent. Instead, the patients' T cells markedly increased immunoglobulin production induced by EBV. In further studies, we determined that the mean frequency of circulating EBV-infected B cells capable of spontaneous outgrowth in vitro was 13 per 10(6) B cells in 7 patients with AIDS and 21 per 10(6) B cells in 10 patients with AIDS-related disorders--figures that were significantly higher than the mean in normal controls (P less than 0.001). Thus, patients with AIDS or AIDS-related disorders may be predisposed to the development of EBV-containing lymphomas, because they have a profound defect of T-cell immunity to EBV and abnormally high numbers of EBV-infected B cells in the circulation.     

The immunoarchitecture of cutaneous pseudolymphoma

The immunoarchitecture of five cutaneous pseudolymphomas was studied by staining serial sections for T- and B-cell and dendritic reticulum cell (DRC) antigens with monoclonal antibodies, and compared with that of reactive lymph nodes and cutaneous lymphoma. In four cases compartmentalization of B and T cells was observed, analogous to findings in reactive lymph nodes. In two of these cases the immunoarchitectural features were strikingly similar to those of reactive lymph nodes. Both had distinct follicles with germinal centers, and in one distinct mantle zone formation was seen. B cells in the follicles were polyclonal, with kappa chain predominance. The germinal centers showed the expected intercellular and/or dendritic pattern of immunoglobulin heavy chain, B2, and DRC-antigen expression. T cells admixed in the germinal centers were overwhelmingly of the T-helper type. The B-cell compartments in the other two cases showed some subtle immunologic evidence of aberrance, but the weight of evidence suggested reactive/aberrant rather than malignant processes. The T-cell compartments in all four cases showed a predominance of T-helper and a minority of T-suppressor/cytotoxic cells. All contrasted with the lymphomas, which showed B-cell monoclonality, markedly deranged T-subset proportions, or novel T-cell phenotypes. Although the main focus of this study was cases involving substantial populations of both B and T cells, preliminary observations were made in one case in which a predominance of T cells and prominent epidermotropism simulated mycosis fungoides. Quantitative ultrastructural analysis in this case suggested a reactive T-cell process. Leu-6-positive Langerhans cells were increased in the epidermis and dermis in all five cases, and in the dermis they were found almost exclusively in T-cell compartments. It is proposed that this distribution is the anatomic correlate to the known functional role of Langerhans cells in antigen processing/presentation and T-cell activation. In the cutaneous "lymph node equivalent," Langerhans cells are analogous to interdigitating reticulum cells of reactive lymph nodes in distribution and, probably, in function. The DRC found in the germinal centers in two cases were probably antigenically identical and functionally analogous to those in germinal centers of reactive lymph nodes. Immunologic phenotyping of serial cutaneous sections may aid in distinguishing reactive from neoplastic lymphoid lesions. Immunoarchitectural analysis promises to be a powerful tool for the study of lymphoproliferative disease.     

Hodgkin's disease, lymphomatoid papulosis, and cutaneous T-cell lymphoma derived from a common T-cell clone.

BACKGROUND. Lymphomatoid papulosis is a benign cutaneous eruption that in 10 to 20 percent of patients is associated with the development of lymphoma. The atypical cells of lymphomatoid papulosis histologically resemble the malignant cells of cutaneous T-cell lymphoma or the Reed-Sternberg cells of Hodgkin's disease. We studied a patient in whom lymphomatoid papulosis developed in 1971, Hodgkin's disease in 1975, and cutaneous T-cell lymphoma in 1985, to determine whether these diseases are clonally related. METHODS. The T-cell-receptor alpha-chain gene was cloned and sequenced from a cell line derived from the advanced-stage cutaneous T-cell lymphoma, and the polymerase chain reaction was used to search for this rearrangement of the alpha-chain gene in tissues obtained earlier that were affected by Hodgkin's disease or lymphomatoid papulosis. RESULTS. The tumor-specific rearrangement of the alpha-chain gene was detected in the patient's earlier tissues affected by lymphomatoid papulosis and Hodgkin's disease, but not in control tissue, including uninvolved tissues from the staging laparotomy for Hodgkin's disease. Cytogenetic studies revealed a translocation, t(8;9)(p22;p24), in cutaneous T-cell lymphoma lines and in a dermatopathic lymph node removed two years before the clinical onset of the cutaneous T-cell lymphoma. Immunohistochemical findings were consistent with an activated T-cell phenotype for the atypical cells of lymphomatoid papulosis, the Reed-Sternberg cells of Hodgkin's disease, and the malignant cells of the T-cell lymphoma. CONCLUSIONS. Lymphomatoid papulosis, Hodgkin's disease, and cutaneous T-cell lymphoma can be derived from a single T-cell clone. A t(8;9) genetic translocation may be involved in the pathogenesis of lymphomatoid papulosis or its progression to malignant disease.     

Adult T-cell leukemia/lymphoma with features of CD30-positive anaplastic large cell lymphoma--a case report.

We experienced a 58-year-old Korean man with adult T-cell leukemia/lymphoma with features of histologically anaplastic large cell lymphoma involving the skin and testis. The patient had cutaneous nodules in both extremities and a palpable right testicular mass. Right orchiectomy was performed and specimens of removed testicle and skin nodules showed immunohistologically anaplastic large cell lymphoma with T-cell phenotype, and CD30 antigen was positive. A human T-cell lymphotropic virus type 1 (HTLV-1) antibody titer was over 1 : 256 and integration of HTLV-1 proviral DNA pX gene was identified in the peripheral blood mononuclear cells and lymphoma tissue by polymerase chain reaction. Peripheral blood and bone marrow did not show any evidence of characteristic neoplastic T-cells.     

gammadelta T-cell lymphoma with tropism for various types of epithelium in a cow.

A 2-year-old Holstein cow developed multiple cutaneous masses, up to 10 cm in diameter, over the neck and trunk. The animal also had neoplastic lesions in internal organs, and epitheliotropism was observed not only in the skin but also in the conjunctiva, mammary glands, trachea, abomasum, small intestine, gall bladder, uterus and urinary bladder. Moreover, the neoplastic cells showed preferential homing to T-zones of lymphatic tissues. Because the lymphoma cells were positive for CD3 but not CD79a, and a few were CD2- or WC1-positive, this lymphoma was thought to be of gammadelta T-cell origin. Helicobacter -like organisms, found in the abomasum and small intestine, were considered to be associated with the severe neoplastic involvement of these organs, on the basis of the intense immunolabelling for major histocompatibility complex class II in the epithelial cells, and the presence of increased numbers of apparently normal intraepithelial T lymphocytes.     

Epstein-Barr virus-associated lymphoproliferative disorder presenting with classical Hodgkin lymphoma and developing as peripheral T-cell lymphoma 9 years later: a case report of composite lymphoma

We describe a patient who was diagnosed with classical Hodgkin lymphoma (CHL) at 67-years-old and peripheral T-cell lymphoma, not otherwise specified (PTCL) at 76-years-old, and died 5 months later. Both tumors showed prominent epithelioid cell reaction admixed with neoplastic cells. Hodgkin and Reed-Sternberg cells in the swollen lymph node were positive for CD30 and EBV-encoded RNA (EBER). PTCL cells in the skin tumor were positive for cytoplasmic CD3ε, CD4 and EBER. A rearrangement band of the T-cell receptor gene was detected in the skin tumor. This case is the first documented EBV-associated composite lymphoma composed of CHL and PTCL. The patient may show the possibility that both EBV infection and/or immunodeficiency induce the development of CHL and PTCL.     

Langerhans cell depletion in gliotoxin-treated murine epidermis.

Langerhans cells (LC) are dendritic antigen presenting cells of bone marrow origin which reside in the suprabasal layer of the epidermis. They express high concentrations of Class II MHC glycoproteins on their plasma membrane and transport cutaneous antigen to local lymph nodes for presentation to helper T cells. They are thus essential for the induction of cutaneous immunity. Gliotoxin is a member of the epipolythiodioxopiperazine (ETP) group of fungal metabolites, derived from the human pathogen Aspergillus fumigatus. It has been shown to have immunomodulating properties in vivo and in vitro, and has been proposed as a potential immunosuppressant for transplantation therapy. Epicutaneous application of gliotoxin reduced the numbers of epidermal LC by 30-35 per cent with an associated morphological change from highly dendritic to a more rounded form. Electron microscopic studies showed selective damage to LC at very low (nM) concentrations of gliotoxin, with no obvious effect on adjacent keratinocytes. LC numbers remained depleted for 13 weeks after initial treatment, suggesting that systemic suppression or prolonged retention of gliotoxin within the skin may play a role in its mechanism of action.     

A Case of Adult T-cell Leukemia/Lymphoma, Histologically Presenting CD30-Positive Large Cell Lymphoma

A 48 year old Japanese woman with adult T-cell leuke-mia/lymphoma (ATLL), histologically presenting CD30 positive large cell lymphoma is reported. The patient, who was from an ATLL endemic area in Japan, had cutaneous nodules in the head, trunk, and extremities, and cervical lymph node swelling; these had been found three months before her admission to our hospital. A biopsy specimen of a skin lesion showed diffuse large cell lymphoma; the lymphoma cells were positively stained with CD30 (Ki 1/ Ber H 2), CD4 (helper T), and CD25 (interleukin 2 receptor) antibodies. Anti HTLV-1 antibody (ATLA) was detected in the serum, and molecular cytogenetic studies of lymphoma cells showed both positive T-cell receptor rearrangement and HTLV-1 specific DNA sequences.     

Differentiation of interdigitating reticulum cells and Langerhans cells in the human skin with T-lymphoid infiltrate. An immunocytochemical and ultrastructural study

The differentiation of two types of T-lymphocyte accessory cells, i.e., interdigitating reticulum cells and Langerhans cells, was studied immunocytochemically and ultrastructurally on cutaneous lesions from patients with mycosis fungoides, a neoplasm of mature T-lymphocytes. In such a condition the lymphoid infiltrate creates, adjacent to the epidermis, a microenvironment in the dermis similar to that of T-cell areas of lymphoid organs. Immunocytochemistry revealed that CD11c+ CD1a- putative monocytic cells co-exist with CD11c+ CD1a+ putative mature accessory cells. By electron microscopy, large numbers of interdigitating reticulum cells in the dermal infiltrate and Langerhans cells in the epidermis were found. Furthermore, monocytes were frequently observed, at times with cells showing intermediate features between monocytes and interdigitating reticulum cells on the one hand and Langerhans cells on the other. In the absence of proliferative phenomena of the above cells, it is conceivable that both interdigitating reticulum cells and Langerhans cells originate from locally migrated monocytes. A possible role of the local tissue micro-environment--namely the T-lymphoid microenvironment for interdigitating reticulum cells and the epidermal microenvironment for Langerhans cells--in inducing the differentiation of monocytes into the two kinds of accessory cells is proposed.     

A case of adult T-cell leukemia/lymphoma, histologically presenting CD30-positive large cell lymphoma.

A 48-year-old Japanese woman with adult T-cell leukemia/lymphoma (ATLL), histologically presenting CD30-positive large cell lymphoma is reported. The patient, who was from an ATLL endemic area in Japan, had cutaneous nodules in the head, trunk, and extremities, and cervical lymph node swelling; these had been found three months before her admission to our hospital. A biopsy specimen of a skin lesion showed diffuse large cell lymphoma; the lymphoma cells were positively stained with CD30 (Ki-1/Ber H-2), CD4 (helper-T), and CD25 (interleukin-2 receptor) antibodies. Anti HTLV-1 antibody (ATLA) was detected in the serum, and molecular cytogenetic studies of lymphoma cells showed both positive T-cell receptor rearrangement and HTLV-1 specific DNA sequences.     

Detection of HTLV-I proviral sequences in CD30-positive large cell cutaneous T-cell lymphomas.

To investigate the possibility that cutaneous T-cell lymphomas of large cell type may be associated with human T-cell leukemia/lymphoma virus type I infection in nonendemic regions, tissue samples from six cases of large cell cutaneous T-cell lymphoma and four cases of small cell cutaneous T-cell lymphoma were screened for the presence of integrated proviral human T-cell leukemia/lymphoma virus type I DNA. Combined use of Southern blot hybridization and enzymatic DNA amplification revealed human T-cell leukemia/lymphoma virus type I-specific sequences in all cases of large cell cutaneous T-cell lymphoma and in none of the cases of small cell cutaneous T-cell lymphoma. These results suggest that in nonendemic areas, a significant proportion of large cell cutaneous T-cell lymphoma cases are associated with human T-cell leukemia/lymphoma virus type I.     

Pagetoid reticulosis (Woringer-Kolopp disease): an immunophenotypic, molecular, and clinicopathologic study.

Pagetoid reticulosis (PR), also known as Woringer-Kolopp disease, is a form of cutaneous T-cell lymphoma that demonstrates striking epidermotropism on histologic examination. We present the histologic, immunologic, and molecular findings for seven patients who had PR. The patients ranged in age from 33 to 67 years. All patients presented with one or several thick plaques involving the distal extremities except for one patient, who presented with a tongue lesion. Immunohistochemical staining of the atypical lymphoid cells demonstrated a T-cell phenotype in all cases. In one of four frozen cases, the neoplastic cells were of T-helper cell phenotype (CD4 positive). Four of seven cases demonstrated a T-cytotoxic/suppressor cell phenotype (CD8 positive). The T-cell subset for the remaining two cases could not be determined. CD30 positivity and a high growth fraction as indicated by staining with Ki-67 were seen in three of seven and three of four cases, respectively. Genotypic analysis performed on three of our cases revealed T-cell receptor (gamma and/or beta) rearrangement, indicating a clonal proliferation. The clinical follow-up ranged from 15 months to 13 years. Four of seven patients are alive and free of disease after treatment with excision or local irradiation. One patient relapsed twice after treatment with radiation and photochemotherapy with 8-methoxypsoralen and UVA and was then lost to follow-up. The lesions of another patient resolved spontaneously but recurred at the same and in an additional site 5 years later. One patient recurred after electron beam therapy. The recurrent lesion improved with radiation therapy and local wound care but never resolved completely. The patient died of unrelated causes. Our findings suggest that PR is a distinct clinicopathologic entity, separate from unilesional mycosis fungoides, demonstrating a slow disease course. The disease is a clonal cutaneous T-cell lymphoma with relatively consistent clinical and histopathologic findings but a heterogeneous immunophenotypic profile.     

Mucosal CD30-positive T-cell lymphoproliferations of the head and neck show a clinicopathologic spectrum similar to cutaneous CD30-positive T-cell lymphoproliferative disorders

CD30-positive T-cell lymphoproliferative disorders are classified as cutaneous (primary cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis) or systemic. As extent of disease dictates prognosis and treatment, patients with skin involvement need clinical staging to determine whether systemic lymphoma also is present. Similar processes may involve mucosal sites of the head and neck, constituting a spectrum that includes both neoplasms and reactive conditions (eg, traumatic ulcerative granuloma with stromal eosinophilia). However, no standard classification exists for mucosal CD30-positive T-cell lymphoproliferations. To improve our understanding of these processes, we identified 15 such patients and examined clinical presentation, treatment and outcome, morphology, phenotype using immunohistochemistry, and genetics using gene rearrangement studies and fluorescence in situ hybridization. The 15 patients (11 M, 4 F; mean age, 57 years) had disease involving the oral cavity/lip/tongue (9), orbit/conjunctiva (3) or nasal cavity/sinuses (3). Of 14 patients with staging data, 7 had mucosal disease only; 2 had mucocutaneous disease; and 5 had systemic anaplastic large cell lymphoma. Patients with mucosal or mucocutaneous disease only had a favorable prognosis and none developed systemic spread (follow-up, 4-93 months). Three of five patients with systemic disease died of lymphoma after 1-48 months. Morphologic and phenotypic features were similar regardless of extent of disease. One anaplastic lymphoma kinase-positive case was associated with systemic disease. Two cases had rearrangements of the DUSP22-IRF4 locus on chromosome 6p25.3, seen most frequently in primary cutaneous anaplastic large cell lymphoma. Our findings suggest mucosal CD30-positive T-cell lymphoproliferations share features with cutaneous CD30-positive T-cell lymphoproliferative disorders, and require clinical staging for stratification into primary and secondary types. Primary cases have clinicopathologic features closer to primary cutaneous disease than to systemic anaplastic large cell lymphoma, including indolent clinical behavior. Understanding the spectrum of mucosal CD30-positive T-cell lymphoproliferations is important to avoid possible overtreatment resulting from a diagnosis of overt T-cell lymphoma.